CN106979984B - The HPLC analytical method of benzyl nicotinate drone salt and application - Google Patents
The HPLC analytical method of benzyl nicotinate drone salt and application Download PDFInfo
- Publication number
- CN106979984B CN106979984B CN201710223163.XA CN201710223163A CN106979984B CN 106979984 B CN106979984 B CN 106979984B CN 201710223163 A CN201710223163 A CN 201710223163A CN 106979984 B CN106979984 B CN 106979984B
- Authority
- CN
- China
- Prior art keywords
- benzyl nicotinate
- drone
- salt
- drone salt
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 title claims abstract description 267
- 150000003839 salts Chemical class 0.000 title claims abstract description 145
- 229950004580 benzyl nicotinate Drugs 0.000 title claims abstract description 133
- 238000004128 high performance liquid chromatography Methods 0.000 title claims abstract description 33
- 238000004458 analytical method Methods 0.000 title claims abstract description 30
- 238000012360 testing method Methods 0.000 claims abstract description 77
- 239000012071 phase Substances 0.000 claims abstract description 48
- 239000000872 buffer Substances 0.000 claims abstract description 38
- 239000013558 reference substance Substances 0.000 claims abstract description 38
- 239000012488 sample solution Substances 0.000 claims abstract description 36
- 238000001514 detection method Methods 0.000 claims abstract description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000012074 organic phase Substances 0.000 claims abstract description 21
- JWKLEQDAKUGXPJ-UHFFFAOYSA-N azanium;acetate;hydrate Chemical compound [NH4+].O.CC([O-])=O JWKLEQDAKUGXPJ-UHFFFAOYSA-N 0.000 claims abstract description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 238000010812 external standard method Methods 0.000 claims abstract description 10
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 8
- 239000000945 filler Substances 0.000 claims abstract description 7
- 239000000523 sample Substances 0.000 claims description 61
- 229960003512 nicotinic acid Drugs 0.000 claims description 17
- 235000001968 nicotinic acid Nutrition 0.000 claims description 17
- 239000011664 nicotinic acid Substances 0.000 claims description 17
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical group N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 16
- 239000005695 Ammonium acetate Substances 0.000 claims description 16
- 229940043376 ammonium acetate Drugs 0.000 claims description 16
- 235000019257 ammonium acetate Nutrition 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 12
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 11
- 239000007791 liquid phase Substances 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 238000007872 degassing Methods 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 4
- 235000019504 cigarettes Nutrition 0.000 claims description 3
- 239000000908 ammonium hydroxide Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 235000021419 vinegar Nutrition 0.000 claims 1
- 239000000052 vinegar Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 33
- 239000012535 impurity Substances 0.000 abstract description 20
- 239000000243 solution Substances 0.000 description 53
- 238000005259 measurement Methods 0.000 description 23
- 239000000047 product Substances 0.000 description 17
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 10
- -1 benzyl Niacin Chemical compound 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 229960004217 benzyl alcohol Drugs 0.000 description 5
- 235000019445 benzyl alcohol Nutrition 0.000 description 5
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 5
- 229940073608 benzyl chloride Drugs 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000000713 mesentery Anatomy 0.000 description 4
- 238000007747 plating Methods 0.000 description 4
- 230000003252 repetitive effect Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 238000004506 ultrasonic cleaning Methods 0.000 description 3
- 208000029422 Hypernatremia Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000000413 hydrolysate Substances 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000011003 system suitability test Methods 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- GVGVUNDFQUSHDM-UHFFFAOYSA-N 1-benzyl-2h-pyridine Chemical compound C=1C=CC=CC=1CN1CC=CC=C1 GVGVUNDFQUSHDM-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 240000000233 Melia azedarach Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- XIUXNVAVANJALH-UHFFFAOYSA-N chloromethylbenzene hydrate Chemical compound O.ClCC1=CC=CC=C1 XIUXNVAVANJALH-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Pyridine Compounds (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Abstract
The invention discloses a kind of HPLC analytical method of benzyl nicotinate drone salt and applications, this method comprises: (a) provides benzyl nicotinate drone salt reference substance solution and test sample solution；(b) benzyl nicotinate drone salt content in step (a) test sample solution is analyzed by external standard method with HPLC-UV, testing conditions are as follows: chromatographic column: using octadecylsilane chemically bonded silica as filler；Mobile phase: being formed with organic phase and acetic acid-ammonium hydroxide buffer, and organic phase is methanol or acetonitrile；Volume ratio is 0:100~80:20；UV detector Detection wavelength: 190~330nm.The present invention alleviates that the prior art is not perfect to the measuring method of benzyl nicotinate drone salt content, result is inaccurate, can not isolate the technical issues of impurity.The content of benzyl nicotinate drone salt can not only be accurately detected using the method for the present invention, precision is good, can efficiently separate out impurity peaks, realizes and controls benzyl nicotinate drone salt production process quality.
Description
Technical field
The present invention relates to the analysis method technical field of benzyl nicotinate drone salt, in particular to a kind of benzyl nicotinate drone
The HPLC analytical method of salt and application.
Background technique
Benzyl nicotinate drone salt (benzyl pyridinium 3-carboxylate, BPC-48) is mainly used in plating plating
Zinc belongs to the main addition composition in zinc-plating additive as zinc-plated intermediate, and can play makes coating crystallization refinement, effectively mentions
The effect of high current density.Entire sour zinc brightener in the market, this product consumption is very big, and application effect is excellent.
The production of BPC-48 is reacted by benzyl chloride, niacin and sodium hydroxide, is had during the reaction not anti-
Niacin, raw material benzyl chloride hydrolysate benzylalcohol and the benzyl chloride by-product answered exist.Although the complete niacin of unreacted is being electroplated
It does not influence to use in the process, but niacin is easily precipitated in system, influences client's perception, it is therefore necessary to limit the quantity it.Benzyl
Alcohol and benzyl ether acted on played in plating it is unknown, but from product purity consider, also should be in production capacity tolerance band as far as possible
Control.Therefore efficiently and rapidly detect impurity and principal product be quite it is necessary to.
And rarely have article report to the detection method of content of BPC-48 in the prior art, also issued without relevant criterion.If
Simple titration method is only used, the deviation of testing result can be very big, although and using simple ultraviolet spectrophotometer method
Its content can be detected, but impurity can not be isolated, impurity can not be analyzed, can not impurity situation to mid-product carry out
Detection.
In view of this, the present invention is specifically proposed.
Summary of the invention
One of the objects of the present invention is to provide a kind of methods with high-efficient liquid phase chromatogram technique analysis benzyl nicotinate drone salt, are
A kind of simple, accurate, easy to spread method, precision is good, accuracy is high.
The second object of the present invention is to provide the HPLC analytical method of drone the salt of benzyl nicotinate described in one kind
Application in benzyl nicotinate drone salt production process in control monitoring and product quality detection.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
A kind of HPLC analytical method of benzyl nicotinate drone salt, comprising the following steps:
(a) benzyl nicotinate drone salt reference substance solution and test sample solution are provided；
(b) benzyl nicotinate drone the salt content in step (a) test sample solution is divided by external standard method with HPLC-UV
Analysis, the testing conditions of high performance liquid chromatography are as follows:
Chromatographic column: using octadecylsilane chemically bonded silica as filler；
Mobile phase: being formed with organic phase and acetic acid-ammonium hydroxide buffer, organic phase and acetic acid-ammonium hydroxide buffer volume ratio
For 0:100~80:20；Organic phase is methanol or acetonitrile；
The Detection wavelength of UV detector: 190~330nm.
Preferably, based on the technical solution of the present invention, organic phase and acetic acid-ammonium hydroxide buffer in the mobile phase
Volume ratio is 10:90~40:60.
Preferably, based on the technical solution of the present invention, the Detection wavelength of the UV detector is 220~300nm.
Further, based on the technical solution of the present invention, the testing conditions of high performance liquid chromatography also wrap in step (b)
It includes:
Flow velocity: 0.3~1.2mL/min；
Column temperature: 10~60 DEG C；
20 μ L of sample volume.
Preferably, based on the technical solution of the present invention, the flow velocity is 0.8~1.1mL/min；The column temperature is 20
~45 DEG C.
Preferably, based on the technical solution of the present invention, the acetic acid-ammonium hydroxide buffer is ammonium acetate solution, acetic acid
The concentration of ammonium salt solution is 0.013mol/L.
Further, based on the technical solution of the present invention, the benzyl nicotinate drone salt reference substance solution using content >=
48.4% benzyl nicotinate drone salt standard items are prepared, and specifically include benzyl nicotinate drone salt standard items flowing phased soln,
It is configured to the reference substance solution that concentration is 10.0mg/mL.
Further, based on the technical solution of the present invention, the preparation of the test sample solution is specifically included benzyl
Niacin drone salt test sample flowing phased soln, is configured to the test sample solution that concentration is 1.0mg/mL.
Preferably, based on the technical solution of the present invention, the HPLC analytical method of benzyl nicotinate drone salt, packet
Include following steps:
(a) buffer and mobile phase are provided: ammonium acetate is soluble in water, the solution that concentration is 0.013mol/L, mistake is made
Filter, it is stand-by to be made buffer；It takes filtered organic phase to mix with buffer by the volume ratio of 10:90~40:60, is made after degassing
It is stand-by at mobile phase；
(b) benzyl nicotinate drone salt reference substance solution and test sample solution are provided: the benzyl nicotinate for being 48.4% by content
Drone salt standard items flowing phased soln, is made the solution that concentration is 10.0mg/mL, and it is stand-by that reference substance solution is made in filtering；By benzyl
Base niacin drone salt test sample flowing phased soln, is made the solution that concentration is 1.0mg/mL, and test sample solution is made in filtering
For use；
(c) it is measured according to following high-efficient liquid phase chromatogram condition:
Chromatographic column: using octadecylsilane chemically bonded silica as filler；
Mobile phase: the mobile phase in step (a)；
The Detection wavelength of UV detector: 220~300nm；
Flow velocity: 0.8~1.1mL/min；
Column temperature: 20~45 DEG C；
20 μ L of sample volume；
(d) external standard method is pressed, the content of benzyl nicotinate drone salt in test sample solution is calculated.
A kind of HPLC analytical method of benzyl nicotinate described in any of the above embodiments drone salt is in benzyl nicotinate drone salt
Application in production process in control monitoring and product quality detection.
Compared to the prior art, beneficial effects of the present invention are as follows:
The present invention utilizes high performance liquid chromatography, cooperates UV detector, with calibration curve method to benzyl nicotinate drone salt content
It is analyzed, alleviates the prior art to the incomplete technical problem of measuring method of benzyl nicotinate drone salt content, dripped compared with soda acid
It is accurate to determine method measurement result, although its content can be detected by alleviating ultraviolet spectrophotometer method, asking for impurity can not be isolated
Topic.The content of benzyl nicotinate drone salt can not only be accurately detected using the method for the present invention, as a result precision is good, and precision is less than
2.7%, accuracy is high, high sensitivity, and can efficiently separate out impurity peaks, realizes to benzyl nicotinate drone salt production process
Control of product quality.In addition, in the method for the present invention sample and mobile phase prepare, whole operation process it is simple and easy, methodological science,
Reliably, controllably, it is suitable for practical application and popularization.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be to needed in the embodiment attached
Figure is briefly described, it should be understood that the following drawings illustrates only certain embodiments of the present invention, therefore is not construed as pair
The restriction of range for those of ordinary skill in the art without creative efforts, can also be according to this
A little attached drawings obtain other relevant attached drawings.
Fig. 1 is the high-efficient liquid phase chromatogram of one benzyl nicotinate of embodiment drone salt reference substance；
Fig. 2 is that one benzyl nicotinate of embodiment drone salt compares linear graph；
Fig. 3 is the high-efficient liquid phase chromatogram of embodiment dibenzyl niacin drone salt reference substance；
Fig. 4 is that embodiment dibenzyl niacin drone salt compares linear graph.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
According to an aspect of the invention, there is provided a kind of HPLC analytical method of benzyl nicotinate drone salt, packet
Include following steps:
(a) benzyl nicotinate drone salt reference substance solution and test sample solution are provided；
(b) benzyl nicotinate drone the salt content in step (a) test sample solution is divided by external standard method with HPLC-UV
Analysis, the testing conditions of high performance liquid chromatography are as follows:
Chromatographic column: using octadecylsilane chemically bonded silica as filler；
Mobile phase: being formed with organic phase and acetic acid-ammonium hydroxide buffer, organic phase and acetic acid-ammonium hydroxide buffer volume ratio
For 0:100~80:20；Organic phase is methanol or acetonitrile；
The Detection wavelength of UV detector: 190~330nm.
Benzyl nicotinate drone salt (BPC-48) is also referred to as 1- benzyl pyridine -3- carboxylate, is a kind of zinc-plated intermediate.
In the present invention, chromatographic column uses octadecylsilane chemically bonded silica column, such as C18 chromatographic column, ODS chromatographic column, preferably
Ground, chromatographic column use Kromasil C18,5 μ, 250mm × 4.6mm orXB-C18,5μ,250mm×4.6mm。
In the present invention, mobile phase is made of organic phase and acetic acid-ammonium hydroxide buffer, wherein organic phase is methanol or acetonitrile；
Acetic acid-ammonium hydroxide buffer be acetic acid-ammonium hydroxide buffer system, pH range be 3~10, for example, 3,3.5,4,4.5,5,5.5,6,
6.5,7,7.5,8,8.5,9,9.5,10 etc.；Organic phase and the typical but non-limiting example of acetic acid-ammonium hydroxide buffer volume ratio
For example 0:100,10:90,20:80,30:70,40:60,50:50,60:40,70:30 or 80:20.
Preferably, organic phase and acetic acid-ammonium hydroxide buffer volume ratio are 0:100~50:50 in mobile phase.
It is further preferred that organic phase and acetic acid-ammonium hydroxide buffer volume ratio are 10:90~50:50 in mobile phase.
In the present invention, the Detection wavelength of UV detector it is typical but non-limiting be, for example, 190nm, 200nm, 210nm,
220nm, 230nm, 240nm, 250nm, 260nm, 270nm, 280nm, 290nm, 300nm, 310nm, 320nm or 330nm.
The prior art has titration and ultraviolet spectrophotometry to the detection of benzyl nicotinate drone salt, is detected and is tied using titration
Fruit accuracy is low, and deviation is larger, although and ultraviolet spectrophotometry can detect its content, impurity can not be separated and be divided
Analysis, it has not been convenient to which the product quality of benzyl nicotinate drone salt production process is controlled.
The HPLC-UV analytic approach that the present invention uses can analyze benzyl nicotinate drone salt content, the better simply soda acid of measurement result
Titration and ultraviolet detection method are more acurrate.This method has many advantages, such as that precision is good, accuracy is high, as long as operator association is molten
(note) sample can be analyzed accurately, can be used for the production process detection and control of product quality of benzyl nicotinate drone salt.
In a preferred embodiment, organic phase and acetic acid-ammonium hydroxide buffer volume ratio are 10:90 in mobile phase
~40:60, such as 10:90,20:80,30:70 or 40:60.
In a preferred embodiment, the Detection wavelength of UV detector is 220~300nm.
By advanced optimizing proportion of mobile phase and Detection wavelength, chromatographic condition is optimized, realizes preferably separation
Effect realizes the optimization of separating degree and the optimization of peak type.
As a preferred embodiment, in step (b) high performance liquid chromatography testing conditions further include: flow velocity: 0.3
~1.2mL/min；Column temperature: 10~60 DEG C；20 μ L of sample volume.
Flow velocity it is typical but non-limiting be, for example, 0.4mL/min, 0.5mL/min, 0.6mL/min, 0.7mL/min,
0.8mL/min, 0.9mL/min, 1.0mL/min, 1.1mL/min or 1.2mL/min.
Typical but non-limiting column temperature is, for example, 10 DEG C, 20 DEG C, 30 DEG C, 40 DEG C, 50 DEG C or 60 DEG C.
The sampling volume of high performance liquid chromatography operation uses 20 μ L quantitative sample injection rings, full ring sample introduction, 80 μ L of sampling volume.
Flow velocity determines the appearance time of sample, and column temperature imitates column and product separation also has certain influence, by flow velocity
With the setting of column temperature, to obtain good separating effect.
In a preferred embodiment, flow velocity is 0.8~1.1mL/min；Column temperature is 20~45 DEG C.
By advanced optimizing flow velocity and column temperature, to obtain preferable appearance time and separating effect.
As a preferred embodiment, acetic acid-ammonium hydroxide buffer is ammonium acetate solution, the concentration of ammonium acetate solution is
0.013mol/L。
Acetic acid-ammonium hydroxide buffer system is directly formulated with ammonium acetate, operates simpler, and the pH value of ammonium acetate is close to 7.
As a preferred embodiment, benzyl nicotinate drone salt reference substance solution uses the benzyl cigarette of content >=48.4%
Sour drone salt standard items are prepared, and specifically include benzyl nicotinate drone salt standard items flowing phased soln, being configured to concentration is
10.0mg/mL reference substance solution.
Wherein, content is mass percentage.
Using content >=48.4% known content benzyl nicotinate drone salt standard items as reference substance, reference substance is made
It is different dense between 0.01mg/mL~5.0mg/mL to be further diluted to concentration with mobile phase for the reference substance solution of 10.0mg/mL
The standard solution for spending gradient obtains standard curve after measuring by above-mentioned chromatographic condition, the correlation of straight line in this concentration range
Coefficient can reach 0.9999.
As a preferred embodiment, the preparation of test sample solution is specifically included benzyl nicotinate drone salt for sample
Product flowing phased soln, is configured to the test sample solution that concentration is 1.0mg/mL.
The range of linearity of calibration curve is 0.01mg/mL~5.0mg/mL, and benzyl nicotinate drone salt test sample is flowed
The content of benzyl nicotinate drone salt in test sample solution can be calculated by external standard method after phase dilution, so obtain benzyl nicotinate drone
The mass fraction of salt test sample.
In a preferred embodiment, the efficient liquid phase chromatographic analysis side as a kind of typical benzyl nicotinate drone salt
Method, comprising the following steps:
(a) buffer and mobile phase are provided: ammonium acetate is soluble in water, the solution that concentration is 0.013mol/L, mistake is made
Filter, it is stand-by to be made buffer；It takes filtered organic phase to mix with buffer by the volume ratio of 10:90~40:60, is made after degassing
It is stand-by at mobile phase；
(b) benzyl nicotinate drone salt reference substance solution and test sample solution are provided: the benzyl nicotinate for being 48.4% by content
Drone salt standard items flowing phased soln, is made the solution that concentration is 10.0mg/mL, and it is stand-by that reference substance solution is made in filtering；It will
Benzyl nicotinate drone salt test sample flowing phased soln, is made the solution that concentration is 1.0mg/mL, and it is molten that test sample is made in filtering
Liquid is stand-by；
(c) it is measured according to following high-efficient liquid phase chromatogram condition:
Chromatographic column: using octadecylsilane chemically bonded silica as filler；
Mobile phase: the mobile phase in step (a)；
The Detection wavelength of UV detector: 220~300nm；
Flow velocity: 0.8~1.1mL/min；
Column temperature: 20~45 DEG C；
20 μ L of sample volume；
(d) external standard method is pressed, the content of benzyl nicotinate drone salt in test sample solution is calculated.
Preferably, in step (a), the preparation method of buffer are as follows: 1g ammonium acetate is dissolved in 1000mL water, is filtered,
Buffer is made.
Preferably, in step (b), the preparation method of benzyl nicotinate drone salt reference substance solution are as follows: be by 500mg content
48.4% benzyl nicotinate drone salt standard items are dissolved in 50mL mobile phase, and reference substance solution is made in filtering.
Preferably, in step (b), the preparation method of benzyl nicotinate drone salt test sample solution are as follows: by the benzyl of 50mg
Niacin drone salt test sample is dissolved in 50mL mobile phase, and test sample solution is made in filtering.
Mobile phase is using preceding ultrasonic degassing.
Mobile phase is prepared using ultrapure water, can select dual pure water distiller or the pure water with amberplex
The gone out ultrapure water of machine.
Preferably, system suitability survey is carried out before carrying out the measurement of benzyl nicotinate drone salt content to the test solution
Examination.
As another aspect of the present invention, a kind of efficient liquid phase chromatographic analysis side of above-mentioned benzyl nicotinate drone salt is provided
Method controls the application in monitoring and product quality detection in benzyl nicotinate drone salt production process.
In order to further appreciate that specific operation process and separating effect of the invention, combined with specific embodiments below and compare
The present invention will be further described in detail for example.
Instrument used in embodiment and reagent are as follows:
Laboratory apparatus:
500 high performance liquid chromatograph (U.S. SSI) of MODEL
LabAlliance HPLC Workstation chromatographic work station
Ultrasonic cleaning machine DS-3120, Tianjin Dong Kang Science and Technology Ltd.
AR2140 electronic balance (1/10000 balance), U.S. Ao Haosi
Drug:
BPC-48 test sample: technical grade, Hubei Jihechang Chemical Industry Technology Co., Ltd.；
BPC-48 reference substance: BPC-48 standard items, 48.4% Ya Te surface modifier company, India ARTEK product of mass fraction
Board；
Methanol/acetonitrile: chromatographically pure, Sinopharm Chemical Reagent Co., Ltd.；
Ammonium acetate: pure, Tianjin Bei Lian fine chemicals development corporation, Ltd. is analyzed；
Other reagents are that analysis is pure.
Instrument used in comparative example and reagent are as follows:
Laboratory apparatus:
UV-2120 ultraviolet specrophotometer
AR2140 electronic balance (1/10000 balance), U.S. Ao Haosi
100ml volumetric flask
250ml volumetric flask
10ml pipette
Cuvette is a pair of
Drug:
BPC-48 test sample: technical grade, Hubei Jihechang Chemical Industry Technology Co., Ltd.；
BPC-48 reference substance: BPC-48 standard items, 48.4% Ya Te surface modifier company, India of mass percentage
ARTEK brand；
Other reagents are that analysis is pure.
Embodiment one
1, the measurement of benzyl nicotinate drone salt
The chromatographic condition of 1.1 high performance liquid chromatographies:
Chromatographic column:XB-C18,5 μ, 250mm × 4.6mm (are furnished withXB-C18 guard column)；
Flow phase composition volume ratio: second nitrile ︰ buffer=10 ︰ 90；Buffer solution is the ammonium acetate solution of 0.013mol/L；
Flow velocity: 0.85mL/min；；
Column temperature: 30 DEG C；
Detector: UV detector；Detection wavelength: 265nm；
20 μ L of sample volume.
The method of 1.2 high performance liquid chromatography measurement benzyl nicotinate drone salt, comprising the following steps:
Buffer and mobile phase are prepared: accurately being weighed 1g ammonium acetate and are dissolved in 50mL beaker, are transferred to 1000mL volumetric flask
After middle use water constant volume, is filtered with 0.45 μm of water system film, it is stand-by that buffer is made；Take 0.45 μm of organic filtered acetonitrile of mesentery with
Buffer is made into mobile phase by the volume ratio of 10:90, is uniformly mixed, and obtains mobile phase with ultrasonic cleaning machine degassing half an hour；
The preparation of reference substance solution: benzyl nicotinate drone the salt standard items that 500mg content is 48.4% are accurately weighed in 50mL
In volumetric flask, with above-mentioned flowing phased soln constant volume, filtered using preceding with 0.2 μm of organic mesentery, for use, the concentration of the solution is
10.0mg/mL；
System suitability test: the above-mentioned flowing phased soln of benzyl nicotinate drone salt standard items accurately is weighed, is made into concentration about
It for the solution of 1.0mg/mL, shakes up, obtains system suitability solution；By system suitability solution with the sample volume sample introduction of 20 μ L into
Row measurement makes benzyl nicotinate drone separating degree between salt peak and impurity peaks be greater than 1.5, and number of theoretical plate is in terms of benzyl nicotinate drone salt peak
5000 should be not less than by calculating, and tailing factor must not cross 2.0；
The preparation of test sample solution: benzyl nicotinate drone the salt test sample (technical grade) for accurately weighing 50mg is held in 50mL
In measuring bottle, with above-mentioned flowing phased soln constant volume, filtered using preceding with 0.2 μm of organic mesentery, for use, the concentration of the solution is
1.0mg/mL；
Measurement: by above-mentioned high performance liquid chromatography chromatographic condition by benzyl nicotinate in external standard method test solution drone
The content of salt.
Fig. 1 is the high-efficient liquid phase chromatogram of one benzyl nicotinate of embodiment drone salt reference substance, benzyl nicotinate drone salt retention time
In 6.7min.
2, the measuring method verifying of benzyl nicotinate drone salt
2.1 linear relationship
Precision measures above-mentioned reference substance solution, is placed in volumetric flask, and mobile phase constant volume shakes up, and obtains mass concentration respectively and is
0.01mg/mL、0.1mg/mL、0.5mg/mL、1.0mg/mL、1.25mg/mL、1.5mg/mL、1.75mg/mL、2mg/mL、3mg/
The linear solvent of mL, 5mg/mL.It being measured according to above-mentioned chromatographic condition, every part of linear solvent measures 5 times, peak area average value is taken, with
Concentration (c) is abscissa, and peak area (A) is ordinate, draws standard curve, and calculate regression equation, the results are shown in Table 1, benzyl
Niacin drone salt compares linear graph (equation of linear regression are as follows: A=705016c-0.6431, R as shown in Figure 22=0.9999).
Table 1 benzyl nicotinate drone salt compares linear relationship result
Seen from table 1, benzyl nicotinate drone salinity has preferable linear, related coefficient within the scope of 0.01~5mg/mL
R2=0.9999.
2.2 measurement result
By the benzyl nicotinate of preparation drone salt test sample solution, measures according to above-mentioned chromatographic condition, calculated by standard curve
Obtain: the mass concentration of benzyl nicotinate drone salt is 0.9734mg/mL, i.e. mass fraction=0.9734 BPC-48 × 48.4%=
47.12%.
2.3 precision test
Precision weighs benzyl nicotinate drone salt standard items 10mg, and solubilizer (mobile phase) makes to dissolve in right amount, is settled to 10mL appearance
In measuring bottle, the standard solution for drone the salt containing benzyl nicotinate that mass concentration is 1mg/mL is made, shakes up, the solution is taken to repeat sample introduction 7
It is secondary, peak area is recorded, sample introduction precision is calculated, the results are shown in Table 2.
2 sample introduction Precision test result of table
As can be seen from Table 2, the RSD% of the peak area of sample introduction precision is 2.65, meet the requirements.
2.4 repetitive test
Precision weighs benzyl nicotinate drone salt test sample 10mg, and solubilizer (mobile phase) makes to dissolve in right amount, is settled to 10mL
Volumetric flask in, be made mass concentration be 1mg/mL drone the salt sample solution containing benzyl nicotinate, shake up, prepare 6 parts of samples altogether with method
Product solution measures the content of benzyl nicotinate drone the salt in every part of sample solution according to the above method, calculates precision, the results are shown in Table 3.
3 repetitive test result of table
Seen from table 3, repeated RSD% is 0.12, is met the requirements.
The shelf-stability of 2.5 test sample solution
Precision weighs benzyl nicotinate drone salt test sample 10mg, and the appearance of 10mL is dissolved and be settled to solvent (mobile phase)
In measuring bottle, be made concentration be 1mg/mL solution, shake up, set and place at room temperature, respectively at 0h, 1h, 2h, 6h, 12h, for 24 hours into
Sample calculates the variation degree of main peak content, the results are shown in Table 4.
The shelf-stability test result of 4 test sample solution of table
By table 4 as it can be seen that under aqueous solution state the peak area of benzyl nicotinate drone salt at any time passage variation it is smaller,
For RSD% less than 8%, solution is preferable in internal stability for 24 hours.
2.6 accuracy --- recovery test
It is appropriate that precision weighs test sample, sets in volumetric flask, respectively with 0.8 times of limit (80%), 1.0 times of limit
(100%), benzyl nicotinate drone salt reference substance is added in 1.2 times of limit (120%) of amount, is dissolved in water and is diluted to scale, shakes up.
It is each to prepare 3 parts, the content of chromatographic condition measurement benzyl nicotinate drone the salt under item is measured according to benzyl nicotinate drone salt content, calculates recycling
Rate and RSD, the results are shown in Table 5.
5 recovery test result of table
By table 5 as it can be seen that the average recovery rate of benzyl nicotinate drone salt is, RSD% 5.42 meets the requirements.
2.7 impurity analysis
By verifying, the peak occurred at 3.7 minutes is raw material niacin, and the peak occurred at 22.8 minutes is raw material benzyl chloride water
Object benzylalcohol is solved, as shown in Figure 1.
2.8 serviceability test
Test sample is taken, mobile phase pH of cushioning fluid, wavelength, flow velocity and column temperature is finely tuned respectively, contains according to benzyl nicotinate drone salt
The method measurement determined under item is measured, investigates the variation degree of benzyl nicotinate drone salt content, measurement result is shown in Table 6.
6 serviceability test result of table
By table 6 as it can be seen that the good tolerance of this chromatographic system, the variation of flow velocity, mobile phase pH of buffer, column temperature, wavelength
The measurement of separation and content to benzyl nicotinate drone salt has not significant impact.
Embodiment two
1, the measurement of benzyl nicotinate drone salt
The chromatographic condition of 1.1 high performance liquid chromatographies:
Chromatographic column: Kromasil C18,5 μ, 250mm × 4.6mm (are furnished with Kromasil guard column)；
Flow phase composition volume ratio: first alcohol ︰ buffer=20 ︰ 80；Buffer solution is the ammonium acetate solution of 0.013mol/L；
Flow velocity: 0.85mL/min；；
Column temperature: 30 DEG C；
Detector: UV detector；Detection wavelength: 265nm；
20 μ L of sample volume.
The method of 1.2 high performance liquid chromatography measurement benzyl nicotinate drone salt, comprising the following steps:
Buffer and mobile phase are prepared: accurately being weighed 1g ammonium acetate and are dissolved in 50mL beaker, are transferred to 1000mL volumetric flask
After middle use water constant volume, is filtered with 0.45 μm of water system film, it is stand-by that buffer is made；Take 0.45 μm of organic filtered methanol of mesentery with
Buffer is made into mobile phase by the volume ratio of 20:80, is uniformly mixed, and obtains mobile phase with ultrasonic cleaning machine degassing half an hour；
The preparation of reference substance solution: with embodiment one；
System suitability test: the above-mentioned flowing phased soln of benzyl nicotinate drone salt standard items accurately is weighed, is made into concentration about
It for the solution of 1.0mg/mL, shakes up, obtains system suitability solution；By system suitability solution with the sample volume sample introduction of 20 μ L into
Row measurement makes benzyl nicotinate drone separating degree between salt peak and impurity peaks be greater than 1.5, and number of theoretical plate is in terms of benzyl nicotinate drone salt peak
5000 should be not less than by calculating, and tailing factor must not cross 2.0；
The preparation of test sample solution: with embodiment one；
Measurement: by above-mentioned high performance liquid chromatography chromatographic condition by benzyl nicotinate in external standard method test solution drone
The content of salt.
Fig. 3 is the high-efficient liquid phase chromatogram for implementing two benzyl nicotinate drone salt reference substances, benzyl nicotinate drone salt retention time
In 5.5min.
2, the measuring method verifying of benzyl nicotinate drone salt
2.1 linear relationship
Precision measures above-mentioned reference substance solution, is placed in volumetric flask, and mobile phase constant volume shakes up, and obtains mass concentration respectively and is
0.01mg/mL、0.1mg/mL、0.5mg/mL、1.0mg/mL、1.25mg/mL、1.5mg/mL、1.75mg/mL、2mg/mL、3mg/
The linear solvent of mL, 5mg/mL.It being measured according to above-mentioned chromatographic condition, every part of linear solvent measures 5 times, peak area average value is taken, with
Concentration (c) is abscissa, and peak area (A) is ordinate, draws standard curve, and calculate regression equation, the results are shown in Table 7, benzyl
Niacin drone salt compares linear relationship chart (equation of linear regression are as follows: A=580397c+15785, R as shown in Figure 42=0.9973).
Table 7 benzyl nicotinate drone salt compares linear relationship result
By table 7 as it can be seen that benzyl nicotinate drone salinity is within the scope of 0.01~5mg/mL, there is preferable linear, related coefficient
R2=0.9973.
2.2 measurement result
By the benzyl nicotinate of preparation drone salt test sample solution, measures according to above-mentioned chromatographic condition, calculated by standard curve
Obtain: the mass concentration of benzyl nicotinate drone salt is 0.9624mg/mL, i.e. mass fraction=0.9624 BPC-48 × 48.4%=
46.58%.
2.3 precision test
Precision weighs benzyl nicotinate drone salt standard items 10mg, and solubilizer (mobile phase) makes to dissolve in right amount, is settled to 10mL appearance
In measuring bottle, the standard solution for drone the salt containing benzyl nicotinate that mass concentration is 1mg/mL is made, shakes up, the solution is taken to repeat sample introduction 7
It is secondary, peak area is recorded, sample introduction precision is calculated, the results are shown in Table 8.
8 sample introduction Precision test result of table
By table 8 as it can be seen that the RSD% of the peak area of sample introduction precision is 1.80, meet the requirements.
2.4 repetitive test
Precision weighs benzyl nicotinate drone salt test sample 10mg, and solubilizer (mobile phase) makes to dissolve in right amount, is settled to 10mL
Volumetric flask in, be made mass concentration be 1mg/mL drone the salt sample solution containing benzyl nicotinate, shake up, prepare 6 parts of samples altogether with method
Product solution measures the content of benzyl nicotinate drone the salt in every part of sample solution according to the above method, calculates precision, the results are shown in Table 9.
9 repetitive test result of table
By table 9 as it can be seen that the RSD% of repeatability is 1.4%, meet the requirements.
The shelf-stability of 2.5 test sample solution
Precision weighs benzyl nicotinate drone salt test sample 10mg, and the capacity of 10mL is dissolved and be settled to solvent (mobile phase)
In bottle, the solution that concentration is 1mg/mL is made, shakes up, sets and place at room temperature, respectively at 0h, 1h, 2h, 6h, 12h, for 24 hours sample introduction,
The variation degree for calculating main peak content, the results are shown in Table 10.
The shelf-stability test result of 10 test sample solution of table
By table 10 as it can be seen that under aqueous solution state the passage of the peak area of benzyl nicotinate drone salt at any time vary less, it is molten
Liquid is preferable in internal stability for 24 hours.
2.6 accuracy --- recovery test
It is appropriate that precision weighs test sample, sets in volumetric flask, respectively with 0.8 times of limit (80%), 1.0 times of limit
(100%), benzyl nicotinate drone salt reference substance is added in 1.2 times of limit (120%) of amount, is dissolved in water and is diluted to scale, shakes up.
It is each to prepare 3 parts, the content of chromatographic condition measurement benzyl nicotinate drone the salt under item is measured according to benzyl nicotinate drone salt content, calculates recycling
Rate and RSD, the results are shown in Table 11.
11 recovery test result of table
By table 11 as it can be seen that the average recovery rate of benzyl nicotinate drone salt is, RSD% 6.46 meets the requirements.
2.7 impurity analysis
By verifying, the peak occurred at 3 minutes is raw material niacin, and the peak occurred at 19.5 minutes is the hydrolysis of raw material benzyl chloride
Object benzylalcohol.
2.8 serviceability test
Test sample is taken, mobile phase pH of cushioning fluid, wavelength, flow velocity and column temperature is finely tuned respectively, contains according to benzyl nicotinate drone salt
The method measurement determined under item is measured, investigates the variation degree of benzyl nicotinate drone salt content, measurement result is shown in Table 12.
12 serviceability test result of table
By table 12 as it can be seen that the good tolerance of this chromatographic system, the variation of flow velocity, mobile phase pH of buffer, column temperature, wavelength
The measurement of separation and content to benzyl nicotinate drone salt has not significant impact.
Comparative example
Ultraviolet specrophotometer measures benzyl nicotinate drone salt, comprising the following steps:
1,0.3000g sample is accurately weighed, is dissolved in distilled water, room temperature constant volume in 250mL volumetric flask is transferred to, uses liquid relief
Pipe measures 10mL into 100mL volumetric flask, room temperature constant volume.Reference substance solution is prepared simultaneously.
2,200~300nm of ultraviolet specrophotometer measurement range is set, using distilled water as blank, examination is measured at 259nm
The absorbance of sample and reference substance.
3, ultraviolet spectrophotometer method measurement result: sample absorbance 0.586 calculates to obtain BPC-48 mass percentage
It is 48.32%.
4, calculation formula
BPC-48%=(ASample/AControl)×(WControl×x/WSample) × 100%
In formula:
ASampleSample absorbance
AControlReference substance absorbance
WControlReference substance sample weighting amount, g
WSampleSample sample weighting amount, g
X- reference substance mass percentage
Conclusion: although the method can detect BPC-48 content, cannot isolate impurity content, can not be to benzyl cigarette
The production of sour drone salt carries out quality control.
To sum up, it can be seen that by the analysis of embodiment and comparative example, on the one hand, can be real using ultraviolet specrophotometer
Now to the detection of BPC-48, but can not remaining raw material niacin to production process, benzyl chloride hydrolysate benzylalcohol situation divide
Analysis, impurity can not be isolated, and analyze its content, can not the impurity situation to mid-product detect；And it uses
This point may be implemented in high performance liquid chromatography, can be to drone the salt of the benzyl nicotinate in sample by using chromatographic condition of the invention
It is separated with impurity, and can rapidly and accurately find out whether impurity content accords with by the impurity peak size of reference standards
Analysis to impurity may be implemented in standardization while analyzing benzyl nicotinate drone salt, help to carry out to benzyl nicotinate drone
The middle control of salt production.
On the other hand, different chromatographic column Kromasil C18 andXB-C18 is also to the separating effect of sample
Different, the retention time of Kromasil C18 is shorter, and appearance faster, can obtain a result in a shorter time, improves detection
Efficiency.
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from of the invention
Many other change and modification can be made in the case where spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (9)
1. a kind of HPLC analytical method of benzyl nicotinate drone salt, which comprises the following steps:
(a) benzyl nicotinate drone salt reference substance solution and test sample solution are provided；
(b) benzyl nicotinate drone the salt content in step (a) test sample solution is analyzed by external standard method with HPLC-UV, it is high
The testing conditions of effect liquid phase chromatogram are as follows:
Chromatographic column: using octadecylsilane chemically bonded silica as filler；
Mobile phase: being formed with organic phase and acetic acid-ammonium hydroxide buffer, and organic phase and acetic acid-ammonium hydroxide buffer volume ratio are 10:
90~40:60；Organic phase is methanol or acetonitrile；
The Detection wavelength of UV detector: 190~330nm.
2. the HPLC analytical method of benzyl nicotinate described in accordance with the claim 1 drone salt, which is characterized in that the purple
The Detection wavelength of external detector is 220~300nm.
3. according to the HPLC analytical method of claim 1-2 described in any item benzyl nicotinates drone salt, feature exists
In the testing conditions of high performance liquid chromatography in step (b) further include:
Flow velocity: 0.3~1.2mL/min；
Column temperature: 10~60 DEG C；
20 μ L of sample volume.
4. the HPLC analytical method of benzyl nicotinate described in accordance with the claim 3 drone salt, which is characterized in that the stream
Speed is 0.8~1.1mL/min；The column temperature is 20~45 DEG C.
5. the HPLC analytical method of benzyl nicotinate described in accordance with the claim 1 drone salt, which is characterized in that the vinegar
Acid-ammonium hydroxide buffer is ammonium acetate solution, and the concentration of ammonium acetate solution is 0.013mol/L.
6. the HPLC analytical method of benzyl nicotinate described in accordance with the claim 1 drone salt, which is characterized in that the benzyl
Base niacin drone salt reference substance solution is prepared using benzyl nicotinate drone the salt standard items of content >=48.4%, is specifically included benzyl
Base niacin drone salt standard items flowing phased soln, is configured to the reference substance solution that concentration is 10.0mg/mL.
7. the HPLC analytical method of benzyl nicotinate described in accordance with the claim 1 drone salt, which is characterized in that the confession
The preparation of test agent solution, which is specifically included, flows phased soln for benzyl nicotinate drone salt test sample, and being configured to concentration is 1.0mg/
The test sample solution of mL.
8. the HPLC analytical method of benzyl nicotinate described in accordance with the claim 1 drone salt, which is characterized in that including with
Lower step:
(a) buffer and mobile phase are provided: ammonium acetate is soluble in water, the solution that concentration is 0.013mol/L is made, filters, system
It is stand-by at buffer；It takes filtered organic phase to mix with buffer by the volume ratio of 10:90~40:60, stream is made after degassing
It is dynamic mutually stand-by；
(b) benzyl nicotinate drone salt reference substance solution and test sample solution are provided: benzyl nicotinate drone the salt for being 48.4% by content
Standard items flowing phased soln, is made the solution that concentration is 10.0mg/mL, and it is stand-by that reference substance solution is made in filtering；By benzyl cigarette
Sour drone salt test sample flowing phased soln, is made the solution that concentration is 1.0mg/mL, and filtering is made test sample solution and waits for
With；
(c) it is measured according to following high-efficient liquid phase chromatogram condition:
Chromatographic column: using octadecylsilane chemically bonded silica as filler；
Mobile phase: the mobile phase in step (a)；
The Detection wavelength of UV detector: 220~300nm；
Flow velocity: 0.8~1.1mL/min；
Column temperature: 20~45 DEG C；
20 μ L of sample volume；
(d) external standard method is pressed, the content of benzyl nicotinate drone salt in test sample solution is calculated.
9. a kind of HPLC analytical method according to claim 1-8 described in any item benzyl nicotinates drone salt is in benzyl
Application in niacin drone salt production process in control monitoring and product quality detection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710223163.XA CN106979984B (en) | 2017-04-07 | 2017-04-07 | The HPLC analytical method of benzyl nicotinate drone salt and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710223163.XA CN106979984B (en) | 2017-04-07 | 2017-04-07 | The HPLC analytical method of benzyl nicotinate drone salt and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106979984A CN106979984A (en) | 2017-07-25 |
| CN106979984B true CN106979984B (en) | 2019-05-10 |
Family
ID=59344304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710223163.XA Active CN106979984B (en) | 2017-04-07 | 2017-04-07 | The HPLC analytical method of benzyl nicotinate drone salt and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106979984B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9023431B2 (en) * | 2011-09-19 | 2015-05-05 | Basf Se | Method for coating light alloy rims |
| CN103320821B (en) * | 2013-07-12 | 2016-08-10 | 贵阳华科电镀有限公司 | A kind of Alkaline Zinc Cobalt Alloy Plating liquid |
| CN103435541B (en) * | 2013-09-09 | 2015-01-14 | 湖北吉和昌化工科技有限公司 | Synthesis method of 1-benzylpyridinium-3-carboxylate |
-
2017
- 2017-04-07 CN CN201710223163.XA patent/CN106979984B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN106979984A (en) | 2017-07-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105606738A (en) | HPLC (High Performance Liquid Chromatography) analysis method for sodium 3,3'-dithiodipropane sulfonate | |
| CN111855856A (en) | A method for simultaneously detecting the contents of sodium azide, sodium nitrite and sodium nitrate in sodium azide synthesis reaction solution | |
| CN104820056A (en) | Method for measuring tert-butyl hydrazine hydrochloride by use of pre-column derivatization-high performance liquid chromatography | |
| CN110849980A (en) | Method for detecting content of enantiomer in isopropyl L-alanine | |
| CN108645923B (en) | Method for simultaneously determining sanshoamides and capsaicin in food | |
| CN102998305A (en) | Method for detecting melamine in raw milk by utilizing chromogenic reaction | |
| CN101122589B (en) | High performance liquid chromatography analysis method of urea and its impurity carbamylurea, methylene biuret | |
| CN111999400A (en) | Method for separating and determining impurities of bulk drugs of baricitinib by using HPLC (high performance liquid chromatography) | |
| CN106979984B (en) | The HPLC analytical method of benzyl nicotinate drone salt and application | |
| CN106932514B (en) | The HPLC analytical method of 3- (benzothiazole -2- sulfydryl)-propane sulfonic acid sodium and application | |
| CN110780002B (en) | High-efficiency low-cost detection method for quantifying essential oil components | |
| CN106290680B (en) | The analysis method of the intermediate S- cyanogen methyl isothiourea of cefmetazole acid | |
| CN108107136B (en) | Method for detecting content of trimethylphenol in 2, 5-dimethylphenol by high performance liquid chromatography | |
| CN117191970A (en) | Method for simultaneously detecting N-bromosuccinimide and N-chlorosuccinimide | |
| CN106872629B (en) | A kind of method of three nitrogen amidine contents in measurement dairy products | |
| CN108318593A (en) | Purine detection method | |
| CN104374861B (en) | The method of the related substance of the western croak bulk drug of a kind of HPLC separation determination Leo | |
| Rezai et al. | Sensitive detection of melamine in infant milk and coffee mate by a buffer mediated extraction and HPLC-PDA analytical method | |
| CN109507306B (en) | A kind of determination method of acetyl tributyl citrate in water-based glue | |
| CN110632186B (en) | Method for measuring vitamin D2 content in vitamin D2 injection by UPCC method | |
| CN113325118A (en) | Method for measuring sodium content in parecoxib sodium | |
| CN115774061A (en) | Method for detecting acetic acid in 1-cyclohexyl piperazine | |
| CN108088929B (en) | Analysis method of L-phenylglycine ethyl dane potassium salt | |
| CN107561169B (en) | Method for distinguishing and quantitatively analyzing triethanolamine p-toluenesulfonate in phenolic resin | |
| CN112034058B (en) | Method for detecting isomer impurities in vincamine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: He Xiaofeng Inventor after: Zhou Shijun Inventor after: Liu Jianshe Inventor after: Yang Wei Inventor after: Huang Kaiwei Inventor after: Song Wenhua Inventor before: He Xiaofeng Inventor before: Zhou Shijun Inventor before: Yang Wei Inventor before: Huang Kaiwei Inventor before: Song Wenhua |