CN105717112B - A kind of detection method of sulphite limit - Google Patents
A kind of detection method of sulphite limit Download PDFInfo
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- CN105717112B CN105717112B CN201610059786.3A CN201610059786A CN105717112B CN 105717112 B CN105717112 B CN 105717112B CN 201610059786 A CN201610059786 A CN 201610059786A CN 105717112 B CN105717112 B CN 105717112B
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- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 title claims abstract description 75
- 238000001514 detection method Methods 0.000 title claims abstract description 31
- 239000000243 solution Substances 0.000 claims abstract description 147
- 239000003814 drug Substances 0.000 claims abstract description 84
- 229940079593 drug Drugs 0.000 claims abstract description 83
- 239000012085 test solution Substances 0.000 claims abstract description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000012086 standard solution Substances 0.000 claims abstract description 43
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims abstract description 38
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 claims abstract description 20
- 229910001626 barium chloride Inorganic materials 0.000 claims abstract description 20
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 103
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 33
- 239000002253 acid Substances 0.000 claims description 20
- 239000000706 filtrate Substances 0.000 claims description 16
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 238000001914 filtration Methods 0.000 claims description 11
- 230000020477 pH reduction Effects 0.000 claims description 9
- 238000012360 testing method Methods 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 238000013100 final test Methods 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 3
- 230000035945 sensitivity Effects 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000013558 reference substance Substances 0.000 abstract description 3
- 238000011109 contamination Methods 0.000 abstract description 2
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 238000000034 method Methods 0.000 description 31
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 18
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 12
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 12
- 230000008569 process Effects 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 8
- 229940001482 sodium sulfite Drugs 0.000 description 8
- 235000010265 sodium sulphite Nutrition 0.000 description 8
- 238000007689 inspection Methods 0.000 description 7
- 239000008213 purified water Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 6
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 5
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 description 5
- 235000019252 potassium sulphite Nutrition 0.000 description 5
- -1 Amino Acid Compound Chemical class 0.000 description 4
- 229910001422 barium ion Inorganic materials 0.000 description 4
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 2
- 231100000716 Acceptable daily intake Toxicity 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- ARSLNKYOPNUFFY-UHFFFAOYSA-L barium sulfite Chemical compound [Ba+2].[O-]S([O-])=O ARSLNKYOPNUFFY-UHFFFAOYSA-L 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960002626 clarithromycin Drugs 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229910001882 dioxygen Inorganic materials 0.000 description 2
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 2
- 229960000815 ezetimibe Drugs 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229960001699 ofloxacin Drugs 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 2
- 229940099427 potassium bisulfite Drugs 0.000 description 2
- 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000370738 Chlorion Species 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000004459 forage Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 229940126589 solid medicine Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/82—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a precipitate or turbidity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
Landscapes
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plasma & Fusion (AREA)
- Engineering & Computer Science (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Abstract
The present invention provides a kind of detection method of sulphite limit, includes the following steps：Step 1, sulphite standard solution is prepared；Step 2, the value of the drug amount of taking w is calculated；Step 3, test solution is prepared；Step 4, contrast solution is prepared；Step 5, test solution and contrast solution are respectively placed in No. 1 colorimetric cylinder and No. 2 colorimetric cylinders；Then, it is separately added into excessive barium chloride solution into test solution and contrast solution, then it is V4 to be settled to volume with water respectively, is fully shaken up, stands 0~120 minute；Ocular estimate observes the muddy muddiness for whether being less than reference substance solution generation that test solution generates；If it is, the content of detected drug sulfite salt is less than the value of weight limit a, detected drug meets the requirements.Advantage is：Drug sulfite salt limit can be detected, have the advantages that easy to operate, high sensitivity, required reagent and equipment cost are low and safe and non-toxic free of contamination.
Description
Technical field
The invention belongs to sulphite detection technique fields, and in particular to a kind of detection method of sulphite limit.
Background technology
Sulphite includes sodium sulfite, sodium hydrogensulfite, potassium bisulfite, Hydros, sodium pyrosulfite, Jiao Ya
Potassium sulfate etc..In drug preparation process, since sulphite is commonly used as raw material or reducing agent, alternatively, when using certain
A bit when degradable reagent (such as thionyl chloride), sulphite can be generated after hydrolysis, therefore, in final drug obtained usually
Sulphite can be remained.
Remaining sulphite has certain harmfulness to human body in drug.For example, patent CN104833639 is described
With the forage feed big white mouse 2 years containing 0.1% sodium sulfite, big white mouse development is suppressed；With the feeding containing 0.1% sodium sulfite
Material feeds big white mouse 2 years, and neuritis, the illnesss such as bone marrow suppression occurs in big white mouse.Open the toxicity waited quietly in sulphite in foods
It is summarized in being summarized with detection method and reports sulphite to respiratory system, reproductive system, digestive system, the circulatory system, nerve
The influence of system and immune system.
Based on the understanding to sulphite toxicity, FAO the and WHO combination food additives Committee of Experts (JECFA) determines
Acceptable daily intake (ADI) is 0.7mg/kg, if being 60kg calculating with average weight of being grown up, human body is daily ingestion of
SO2Amount must not exceed 42mg, and harm otherwise will be brought to human body.And for drug, different exploration projects is based on practical need
It wants, it will usually the remaining highest limitation of sulphite is formulated, to ensure the safety in utilization of drug.
Therefore, in drug preparation process, whether drug sulfite salt residual actual amount how is fast and accurately detected
It is limited the quantity in highest hereinafter, being of great significance.
In drug detection technique field,《Chinese Pharmacopoeia》In version four in 2015 and uncharged sulphite limit it is logical
With inspection technique, the general reviewing party of the foreign pharmacopeias such as United States Pharmacopeia, European Pharmacopoeia, Japanese Pharmacopoeia also uncharged sulphite limit
Method.But sulfate limit test method is recorded in domestic Extra Pharmacopoeia Martindale, specific method is：In the test solution being acidified through hydrochloric acid
With barium chloride solution is added in contrast solution, the muddy degree by comparing two parts of solution judges the content of sulfate in test sample
Whether regulation is met, and this method ripe sulfate limit test for being applied to various drugs, is a kind of general method, tool
There are easy to operate, high sensitivity, favorable reproducibility, be easy and fast to judge.Sulfate limit test method in domestic Extra Pharmacopoeia Martindale
Theoretical foundation to be barium ions and sulfate ion can generate barium sulfate in water, and barium sulfate is a kind of salt being insoluble in water,
The ionic product K of its ion at normal temperaturesSPAbout 1 × 10-10Once containing sulfate ion in solution, generated immediately with barium ions white
Color is muddy, can be distinguished by the way that naked eyes are clear, and this method is easy to operate, high sensitivity.
And barium sulfite slightly soluble in water, solubility at 25 DEG C in water is 0.011mg/mL, ionic product KspAbout 5.3
×10-7, and barium sulfite solubility bigger in acid condition, therefore, sulfate limit test method is not particularly suited for sulfurous acid
How salt limit test, fast and accurately detect whether drug sulfite salt residual quantity meets the requirements, be at present there is an urgent need to
It solves the problems, such as.
Invention content
In view of the defects existing in the prior art, the present invention provides a kind of detection method of sulphite limit, can effectively solve
The certainly above problem.
The technical solution adopted by the present invention is as follows：
An object of the present disclosure provides a kind of detection method of sulphite limit, the detection method of the sulphite limit
It is in colorless and transparent drug for test solution obtained in detecting step 3；
Include the following steps：
Step 1, sulphite standard solution is prepared；Wherein, sulphite standard solution is with SO2A concentration of c is counted, unit is
μg/ml；
Step 2, it is calculated as follows to obtain the value of the drug amount of taking w, unit g：
Wherein：B is to test pre-designed sulphite standard solution to take volume, units/ml；
A is to be detected drug sulfite salt with SO2The weight limit of meter, is indicated with %；
Step 3, test solution is prepared：
Step 3.1, the value for the drug amount of taking being calculated by step 2, precision weigh drug；
Step 3.2, appropriate amount of water, shake well is added to make it dissolve into drug, it is such as insoluble, it should filter, take filtrate；
Step 3.3, whether the solution that judgment step 3.2 obtains is alkalinity, if it is, dilute hydrochloric acid is added dropwise extremely into solution
It is neutral；Then step 3.4 is executed；Otherwise, step 3.4 is directly executed；
Step 3.4, it is V1 the solution that step 3.3 obtains to be settled to volume with water；Add the dilute hydrochloric acid that volume is V2
Acidification is carried out, acid solution is obtained；
Step 3.5, whether the solution that judgment step 3.4 obtains is clear solution, if it is not, then filtration step 3.4 obtains
Solution, obtain clear solution；Then step 3.6 is executed；Otherwise, step 3.6 is directly executed；
Step 3.6, whether the clear solution that judgment step 3.5 obtains is in colorless and transparent, if so, thening follow the steps
3.7；
Step 3.7, the hydrogen peroxide of 3%~30% mass fraction is added dropwise in the solution obtained to step 3.5, hydrogen peroxide is added
Volume be V3, shake up, by be added hydrogen peroxide, by the sulphite complete oxidation in acid solution be sulfate, so far match
Final test solution is made；
Step 4, contrast solution is prepared：
Step 4.1, by the value of b used by step 2, the step 1 that precision measures corresponding volume prepares obtained sulfurous acid
Salt standard solution；
Step 4.2, it is V1 the sulphite standard solution measured to be settled to volume with water, and then, volume, which is added, is
The dilute hydrochloric acid of V2 carries out acidification, obtains acid solution；
Step 4.3, the hydrogen peroxide of 3%~30% mass fraction, hydrogen peroxide are added dropwise in the acid solution obtained to step 4.2
The volume of addition is V3, is shaken up, and so far prepares and obtains final contrast solution；
Step 5, the contrast solution that the test solution and step 4 that step 3 obtains obtain is respectively placed in No. 1 colorimetric cylinder and 2
In number colorimetric cylinder；Then, excessive barium chloride solution is separately added into test solution and contrast solution, then fixed with water respectively
It is V4 to hold to volume, is fully shaken up, and stands 0~120 minute；Ocular estimate observe that test solution generates it is muddy whether less than pair
The muddiness generated according to solution；If it is, the content of detected drug sulfite salt is less than the value of weight limit a, it is detected
The drug of survey meets the requirements；Otherwise, the content of detected drug sulfite salt is higher than the value of weight limit a, detected
Drug is undesirable.
Preferably, in step 1, the process for preparation of sulphite standard solution is specially：
Step 1.1, accurate to weigh the sulphite for being dissolved in water；
Step 1.2, add purifying water dissolution sulphite, and quantify dilution preparation and obtain the sulphite standard of a concentration of c
Solution.
Preferably, in step 1.1, the sulphite weighed is containing inferior sulfate radical or bisulfite and to be dissolved in water
Salt.
Preferably, in step 1.1, the sulphite weighed is sodium sulfite, sodium hydrogensulfite, potassium sulfite or sulfurous
Potassium hydrogen phthalate.
Preferably, in step 1.1, the concentration for the sulphite standard solution prepared is (with SO2Meter) it is 10~500 μ
g/ml。
Preferably, in step 2, the value of b is 1ml~10ml；
In step 3.6 and step 4.2, after dilute hydrochloric acid progress acidification is added, obtained acid solution is in obviously acid
Property, pH value is not more than 2.0；
The barium chloride solution being added in step 5 is the barium chloride solution that mass fraction is 25%, the volume of addition be 2ml~
10ml；
V1 is 30~40ml；V3 is 1ml~5ml；V4 is 50ml.
Preferably, the drug detected is solid or solution.
Second purpose of the invention is to provide a kind of detection method of sulphite limit, the detection side of the sulphite limit
It is with coloured drug that method, which is used for test solution obtained in detecting step 3,；
Include the following steps：
Step 1, sulphite standard solution is prepared；Wherein, sulphite standard solution is with SO2A concentration of c is counted, unit is
μg/ml；
Step 2, it is calculated as follows to obtain the value of the drug amount of taking w, unit g：
Wherein：B is to test pre-designed sulphite standard solution to take volume, units/ml；
A is to be detected drug sulfite salt with SO2The weight limit of meter, is indicated with %；
Step 3, test solution A and test solution B is prepared：
Test solution A and test solution B is all made of following manner preparation：
Step 3.1, the value for the drug amount of taking being calculated by step 2, precision weigh drug；
Step 3.2, appropriate amount of water, shake well is added to make it dissolve into drug, it is such as insoluble, it should filter, take filtrate；
Step 3.3, whether the solution that judgment step 3.2 obtains is alkalinity, if it is, dilute hydrochloric acid is added dropwise extremely into solution
It is neutral；Then step 3.4 is executed；Otherwise, step 3.4 is directly executed；
Step 3.4, it is V1 the solution that step 3.3 obtains to be settled to volume with water；Add the dilute hydrochloric acid that volume is V2
Acidification is carried out, acid solution is obtained；
Step 3.5, whether the solution that judgment step 3.4 obtains is clear solution, if it is not, then filtration step 3.4 obtains
Solution, obtain clear solution；Then step 3.6 is executed；Otherwise, step 3.6 is directly executed；
Step 3.6, whether the clear solution that judgment step 3.5 obtains carries color, if so, thening follow the steps 3.7；
Step 3.7, the hydrogen peroxide of 3%~30% mass fraction is added dropwise in the solution obtained to step 3.5, hydrogen peroxide is added
Volume be V3, shake up, by be added hydrogen peroxide, by the sulphite complete oxidation in acid solution be sulfate, so far match
Final test solution is made；
Step 4, contrast solution is prepared：
Step 4.1, excessive barium chloride solution is added into test solution A, fully shakes up and stands, judges that solution is
No aobvious muddiness, if it is, repeated filtration, until obtaining clear filtrate；
Step 4.2, by the value of b used by step 2, the step 1 that precision measures corresponding volume prepares obtained sulfurous acid
Salt standard solution；And the sulphite standard solution of measurement is added in the clear filtrate that step 4.1 obtains；
Step 4.3, the hydrogen peroxide of 3%~30% mass fraction, hydrogen peroxide are added dropwise in the acid solution obtained to step 4.2
The volume of addition is V3, is shaken up, and so far prepares and obtains final contrast solution；
Step 5, the contrast solution that the test solution B and step 4 that step 3 obtains are obtained is respectively placed in No. 1 colorimetric cylinder and 2
In number colorimetric cylinder；Then, it is separately added into excessive barium chloride solution into test solution B and contrast solution, then uses water respectively
It is V4 to be settled to volume, is fully shaken up, and stands 0~120 minute；Whether the muddiness that ocular estimate observation test solution generates is less than
The muddiness that reference substance solution generates；If it is, the content of detected drug sulfite salt is less than the value of weight limit a,
Detected drug meets the requirements；Otherwise, the content of detected drug sulfite salt is higher than the value of weight limit a, is detected
The drug of survey is undesirable.
The detection method of sulphite limit provided by the invention has the following advantages：
(1) drug sulfite salt limit can be detected, there is easy to operate, high sensitivity, required reagent and set
Standby at low cost and safe and non-toxic free of contamination advantage.
(2) total amount of the sulphite and bisulfites in detection drug can be merged whether beyond with SO2The weight of meter
Measure limit.
Description of the drawings
Fig. 1 is the flow diagram of the detection method of sulphite limit provided by the invention；
Fig. 2 is the process for preparation flow diagram of test solution provided by the invention.
Specific implementation mode
In order to make the technical problems, technical solutions and beneficial effects solved by the present invention be more clearly understood, below in conjunction with
Accompanying drawings and embodiments, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein only to
It explains the present invention, is not intended to limit the present invention.
The present invention provides a kind of detection method of sulphite limit, and the detection method of the sulphite limit can be quickly smart
Whether the content of true detection drug sulfite salt meets regulation.It is emphasized that the present invention relates to sulphite,
Unless otherwise indicated, the salt containing inferior sulfate radical had both been included, and had also included the salt containing bisulfite, that is to say, that adopt
With the method for the present invention, whether the total amount of detectable drug sulfite root and bisulfite is in limits.
Whether the detection method of sulphite limit provided by the invention has face after being dissolved in water according to detected drug
Color, and two kinds of detection methods are divided into, certainly, the principle of both detection methods is almost the same, below to both detection sides
Method introduces explanation respectively：
First method：It is in colorless and transparent drug to detect test solution
Since the drug that the present invention detects can be solid, or liquid；Therefore, when drug is solid, this law
Suitable for the detection to solid medicine；When drug is liquid, this law is suitable for the detection to liquid drug.
Include the following steps：
Step 1, sulphite standard solution is prepared；Wherein, sulphite standard solution is with SO2A concentration of c is counted, unit is
μg/ml；
In this step, the process for preparation of any standard solution in the prior art can be used, an example is set forth below：
Step 1.1, accurate to weigh the sulphite for being dissolved in water；
Sulphite herein is containing inferior sulfate radical or bisulfite and to be dissolved in the salt of water, including but not limited to sub-
Sodium sulphate, sodium hydrogensulfite, potassium sulfite or potassium bisulfite etc..
In this step, the concentration of prepared sulphite standard solution can be arbitrary value, from the perspective of from drug detection angles,
General concentration of standard solution is generally 1 μ g/ml, 2 μ g/ml, 5 μ g/ml, 10 μ g/ml, 50 μ g/ml, 100 μ g/ml.For this
Invention can consider the combination energy of sulfate ion and barium ions as a preferred method, between 10~500 μ g/ml
Power is not counting very strong, and less than the binding ability of silver ion and chlorion, therefore concentration of standard solution should be appropriate larger, according to medicine
The requirement of allusion quotation, usual concentration are formulated as 100 μ g/ml.
Step 1.2, add purifying water dissolution sulphite, and quantify dilution preparation and obtain the sulphite standard of a concentration of c
Solution.
Step 2, it is calculated as follows to obtain the value of the drug amount of taking w, unit g：
Wherein：B is to test pre-designed sulphite standard solution to take volume, units/ml；
A is to be detected drug sulfite salt with SO2The weight limit of meter, is indicated with %；
0.000001：The conversion coefficient that result of calculation is converted into gram by microgram.
It is required according to disparity items, b selects different numerical value, for example, an if project demand drug sulfite salt
Content maximum value is with SO2It is calculated as 0.02%, then a values are 0.02%.
Sensitivity when in view of comparison and operability, b values not preferably less than 1ml are generally also not above 10ml.
Such as：Certain drug sulfite salt or bisulfites are set (with SO2Meter) weight limit be 0.02%, setting
Taking for standard solution determines volume for 5ml, a concentration of 100 μ g/ml of sulphite standard solution；Then the drug amount of taking is 2.5g
Step 3, test solution is prepared：
Step 3.1, the value for the drug amount of taking being calculated by step 2, precision weigh drug；
Step 3.2, appropriate amount of water, shake well is added to make it dissolve into drug, it is such as insoluble, it should filter, take filtrate；
Step 3.3, whether the solution that judgment step 3.2 obtains is alkalinity, if it is, dilute hydrochloric acid is added dropwise extremely into solution
It is neutral；Then step 3.4 is executed；Otherwise, step 3.4 is directly executed；
Step 3.4, it is V1 the solution that step 3.3 obtains to be settled to volume with water；Add the dilute hydrochloric acid that volume is V2
Acidification is carried out, acid solution is obtained；
In this step, the dilute hydrochloric acid being added is usually the hydrochloric acid that mass fraction is 10%, and the purpose that dilute hydrochloric acid is added is
So that solution acidification, excluding carbonate etc. can be with the barium ions interference that also sedimentable anion detects this law.It is added
Sample solution should be in obviously acidity after dilute hydrochloric acid, and pH value should be not more than 2.0.
Step 3.5, whether the solution that judgment step 3.4 obtains is clear solution, if it is not, then filtration step 3.4 obtains
Solution, obtain clear solution；Then step 3.6 is executed；Otherwise, step 3.6 is directly executed；
Step 3.6, whether the clear solution that judgment step 3.5 obtains is in colorless and transparent, if so, thening follow the steps
3.7；
Step 3.7, the hydrogen peroxide of 3%~30% mass fraction is added dropwise in the solution obtained to step 3.5, hydrogen peroxide is added
Volume be V3, shake up, by be added hydrogen peroxide, by the sulphite complete oxidation in acid solution be sulfate, so far match
Final test solution is made；
In this step, the effect of hydrogen peroxide, which is added, is：Sulphite or bisulfites is set to be fully oxidized generation sulfuric acid
Salt, chemical reaction is by 1:What 1 molar ratio carried out.
SO2~SO3 2-(HSO3 -)~H2O2~SO4 2-
The minimum addition k (g) of hydrogen peroxide should meet following equation：
The calculation formula of k is：
Wherein：b：Standard solution is added (with SO2Count a concentration of 100 μ g/ml) volume (units/ml)
d：The mass fraction of hydrogen peroxide, is indicated with %
Such as：The standard solution of addition is 5ml, and the mass fraction of hydrogen peroxide is 30%, then the minimum addition of hydrogen peroxide
For：
The density of hydrogen peroxide is close to 1g/ml at room temperature, therefore needs 0.000885ml, that is, less than 1 μ l.So only needing
Add 3%~30% 1~5ml of hydrogen peroxide, can ensure that hydrogen peroxide is significantly excessive under any circumstance, can by sulphite or
Bisulfites is fully oxidized generation sulfate.
Herein it should be noted that if drug itself does not have reproducibility, when the standard solution of 100 μ g/ml measures
And when 1~10ml is added, mass fraction is that 1~5ml is added in 3%~30% hydrogen peroxide, can guarantee that hydrogen peroxide is significantly excessive, from
And realize the detection method of the present invention.But if drug itself has reproducibility, drug can react with hydrogen peroxide, cause by
The sulphite or bisulfites of detection cannot be reacted with hydrogen peroxide, to cannot achieve the present invention.Therefore, the present invention provides
Detection method, be only applicable to be detected the drug without reproducibility.
Core of the invention principle is that the inferior sulfate radical in drug is completely oxidized to sulfate radical, chemically, every strong oxygen
Agent can realize this requirement, such as potassium permanganate, hypochlorous acid, manganese dioxide etc.；But the present invention finally uses visual colorimetry
Judge, therefore oxidant and its reduzate should not should not also introduce other ingredients that may interfere with any color.Due to double
For oxygen water sheet as colourless transparent liquid, reduzate is water, identical with the background of this law, be also not introduced into other it is any at
Point, therefore hydrogen peroxide is best oxidant.
Step 4, contrast solution is prepared：
Step 4.1, by the value of b used by step 2, the step 1 that precision measures corresponding volume prepares obtained sulfurous acid
Salt standard solution；
Step 4.2, it is V1 the sulphite standard solution measured to be settled to volume with water, and then, volume, which is added, is
The dilute hydrochloric acid of V2 carries out acidification, obtains acid solution；
Step 4.3, the hydrogen peroxide of 3%~30% mass fraction, hydrogen peroxide are added dropwise in the acid solution obtained to step 4.2
The volume of addition is V3, is shaken up, and so far prepares and obtains final contrast solution；
Herein, to ensure the comparativity of follow-up contrast solution and test solution, used preparation when contrast solution is prepared
Process to ensure as possible it is consistent with the correlated process that test solution is prepared, for example, step 4.2 constant volume and step 3.3 are determined
Volume product is identical as possible, and the dilute hydrochloric acid volume that step 4.2 is added and the dilute hydrochloric acid volume that step 3.3 is added are identical as possible.Step
The dioxygen water volume that the 4.3 dioxygen water volumes being added and step 3.7 are added is identical as possible.
Step 5, the contrast solution that the test solution and step 4 that step 3 obtains obtain is respectively placed in No. 1 colorimetric cylinder and 2
In number colorimetric cylinder；Then, excessive barium chloride solution is separately added into test solution and contrast solution, then fixed with water respectively
It is V4 to hold to volume, is fully shaken up, and stands 0~120 minute；Ocular estimate observe that test solution generates it is muddy whether less than pair
The muddiness generated according to product solution；If it is, the content of detected drug sulfite salt is less than the value of weight limit a, quilt
The drug of detection meets the requirements；Otherwise, the content of detected drug sulfite salt is higher than the value of weight limit a, is detected
Drug it is undesirable.
Second method：Test solution obtained is with coloured drug in detecting step 3
In this method, sulphite standard solution process for preparation and test solution process for preparation and first method are complete
It is exactly the same.This will not be detailed here.
Include the following steps：
Step 1, sulphite standard solution is prepared；Wherein, sulphite standard solution is with SO2A concentration of c is counted, unit is
μg/ml；
Step 2, it is calculated as follows to obtain the value of the drug amount of taking w, unit g：
Wherein：B is to test pre-designed sulphite standard solution to take volume, units/ml；
A is to be detected drug sulfite salt with SO2The weight limit of meter, is indicated with %；
Step 3, test solution A and test solution B is prepared：
Test solution A and test solution B is all made of following manner preparation：
Step 3.1, the value for the drug amount of taking being calculated by step 2, precision weigh drug；
Step 3.2, appropriate amount of water, shake well is added to make it dissolve into drug, it is such as insoluble, it should filter, take filtrate；
Step 3.3, whether the solution that judgment step 3.2 obtains is alkalinity, if it is, dilute hydrochloric acid is added dropwise extremely into solution
It is neutral；Then step 3.4 is executed；Otherwise, step 3.4 is directly executed；
Step 3.4, it is V1 the solution that step 3.3 obtains to be settled to volume with water；Add the dilute hydrochloric acid that volume is V2
Acidification is carried out, acid solution is obtained；
Step 3.5, whether the solution that judgment step 3.4 obtains is clear solution, if it is not, then filtration step 3.4 obtains
Solution, obtain clear solution；Then step 3.6 is executed；Otherwise, step 3.6 is directly executed；
Step 3.6, whether the clear solution that judgment step 3.5 obtains carries color, if so, thening follow the steps 3.7；
Step 3.7, the hydrogen peroxide of 3%~30% mass fraction is added dropwise in the solution obtained to step 3.5, hydrogen peroxide is added
Volume be V3, shake up, by be added hydrogen peroxide, by the sulphite complete oxidation in acid solution be sulfate, so far match
Final test solution is made；
Step 4, contrast solution is prepared：
Step 4.1, excessive barium chloride solution is added into test solution A, fully shakes up and stands, judges that solution is
No aobvious muddiness, if it is, repeated filtration, until obtaining clear filtrate；
Step 4.2, by the value of b used by step 2, the step 1 that precision measures corresponding volume prepares obtained sulfurous acid
Salt standard solution；And the sulphite standard solution of measurement is added in the clear filtrate that step 4.1 obtains；
Step 4.3, the hydrogen peroxide of 3%~30% mass fraction, hydrogen peroxide are added dropwise in the acid solution obtained to step 4.2
The volume of addition is V3, is shaken up, and so far prepares and obtains final contrast solution；
Herein, obtained test solution is prepared due to step 3 and carries color, the control employed in this step
The process for preparation of solution is different from first method.
This step cardinal principle is：
Excessive barium chloride solution is added into test solution A, the sulfuric acid that can will may contain in test solution A
Root, inferior sulfate radical, bisulfite etc. are completely converted into precipitation, after filtering precipitation, obtain a both without any interference
Ion, color and background solution identical with test solution.Subsequent process is essentially identical with first method.
Step 5, the contrast solution that the test solution B and step 4 that step 3 obtains are obtained is respectively placed in No. 1 colorimetric cylinder and 2
In number colorimetric cylinder；Then, it is separately added into excessive barium chloride solution into test solution B and contrast solution, then uses water respectively
It is V4 to be settled to volume, is fully shaken up, and stands 0~120 minute；Whether the muddiness that ocular estimate observation test solution generates is less than
The muddiness that reference substance solution generates；If it is, the content of detected drug sulfite salt is less than the value of weight limit a,
Detected drug meets the requirements；Otherwise, the content of detected drug sulfite salt is higher than the value of weight limit a, is detected
The drug of survey is undesirable.
Several embodiments are set forth below：
The inspection method of 1 Ofloxacin bulk pharmaceutical chemicals sulfite salt limit of embodiment：
(1) precision weighs anhydrous sodium sulfite 196.9mg and (is equivalent to the SO containing 100mg2), it sets in 100ml measuring bottles, adds pure
Change water dissolution and be diluted to scale, shakes up；Precision measures 1ml, sets in 10ml measuring bottles, purified water is added to be diluted to scale, shake up, and makees
(contain SO for standard sodium sulfite solution2A concentration of 100 μ g/ml).
(2) precision weighs Ofloxacin bulk pharmaceutical chemicals 1.0g, and water 30ml, shake well is added to obtain yellow transparent solution, will filter
Liquid is set in 50ml nessler colorimetric tubes, and the dilute hydrochloric acid 2ml of 10% mass fraction is added, and is added 30% hydrogen peroxide 2ml, is shaken up, as examination
Product solution.Prepare a test solution again with method.
(3) a test solution is taken, 30% hydrogen peroxide 2ml is added, adds 25% barium chloride solution 5ml, stands 10 minutes, mistake
Filter, takes filtrate to set in 50ml nessler colorimetric tubes.Standard sodium sulfite solution 2ml is added into filtrate, then adds 30% hydrogen peroxide
2ml shakes up, as contrast solution, is denoted as A pipes.
(4) another test solution is taken, B pipes are denoted as.
(5) it is separately added into 25% barium chloride solution 5ml into A pipes and B pipes, is diluted with water to 50ml, fully shakes up, places
10 minutes, with setting in black background, from above colorimetric cylinder downwards, compare, the muddiness that B pipes generate must not be richer than the generation of A pipes
Muddiness (limit 0.02%).
The inspection method of 2 Ezetimibe bulk pharmaceutical chemicals sulfite salt limit of embodiment, includes the following steps：
(1) precision weighs anhydrous sodium sulfite 196.9mg and (is equivalent to the SO containing 100mg2), it sets in 100ml measuring bottles, adds pure
Change water dissolution and be diluted to scale, shakes up；Precision measures 1ml, sets in 10ml measuring bottles, purified water is added to be diluted to scale, shake up, and makees
(contain SO for standard sodium sulfite solution2A concentration of 100 μ g/ml).
(2) precision weighs Ezetimibe bulk pharmaceutical chemicals 1.0g, adds appropriate amount of water, shake well, filtering that filtrate is set 50ml Na Shi
In colorimetric cylinder, 40ml is added water to, adds dilute hydrochloric acid 2ml, adds 20% hydrogen peroxide 3ml, shakes up, as test solution.
(3) standard sodium sulfite solution 1ml is taken, is set in 50ml nessler colorimetric tubes, adds water to make into about 40ml, adds dilute hydrochloric acid
2ml adds 20% hydrogen peroxide 3ml, shakes up, as contrast solution.
(4) it is separately added into 25% barium chloride solution 4ml in test solution and contrast solution, is diluted with water to 50ml,
It fully shakes up, places 15 minutes, with setting in black background, from above colorimetric cylinder downwards, compare, what test solution generated
White opacity must not be denseer (limit 0.01%).
The inspection method of 3 gelatin hollow capsule shell sulfite salt limit of embodiment, includes the following steps：
(1) precision weighs anhydrous potassium sulfite 246.9mg and (is equivalent to the SO containing 100mg2), it sets in 100ml measuring bottles, adds pure
Change water dissolution and be diluted to scale, shakes up；Precision measures 1ml, sets in 10ml measuring bottles, purified water is added to be diluted to scale, shake up, and makees
(contain SO for standard potassium sulfite solution2A concentration of 100 μ g/ml).
(2) precision weighs gelatin hollow capsule shell 2.0g, adds appropriate amount of water, shake well, filtration that filtrate is set 50ml Na Shi
In colorimetric cylinder, water is added to make into 40ml, add dilute hydrochloric acid 2ml, added 30% hydrogen peroxide 2ml, shake up, as test solution.
(3) standard potassium sulfite solution 2ml is taken, is set in 50ml nessler colorimetric tubes, is added water to make into about 40ml, add dilute hydrochloric acid
2ml adds 30% hydrogen peroxide 2ml, shakes up, as contrast solution.
(4) it is separately added into 25% barium chloride solution 5ml in test solution and contrast solution, is diluted with water to 50ml,
It fully shakes up, places 8 minutes, with setting in black background, from above colorimetric cylinder downwards, compare, what test solution generated
White opacity must not be denseer (limit 0.01%).
The inspection method of 4 Amino Acid Compound Injection sulfite salt limit of embodiment, includes the following steps：
(1) precision weighs sodium hydrogensulfite 162.5mg and (is equivalent to the SO containing 100mg2), it sets in 100ml measuring bottles, adds purifying
Water dissolution is simultaneously diluted to scale, shakes up；Precision measures 1ml, sets in 10ml measuring bottles, purified water is added to be diluted to scale, shake up, as
Standard solution of sodium bisulfite (contains SO2A concentration of 100 μ g/ml).
(2) precision weighs Amino Acid Compound Injection 40.0g, sets in 50ml nessler colorimetric tubes, adds dilute hydrochloric acid 2ml, adds
30% hydrogen peroxide 2ml, shakes up, as test solution.
(3) standard solution of sodium bisulfite 2ml is taken, is set in 50ml nessler colorimetric tubes, adds water to make into about 40ml, adds dilute hydrochloric acid
2ml adds 30% hydrogen peroxide 2ml, shakes up, as contrast solution.
(4) it is separately added into 25% barium chloride solution 4ml in test solution and contrast solution, is diluted with water to 50ml,
It fully shakes up, places 5 minutes, with setting in black background, from above colorimetric cylinder downwards, compare, what test solution generated
White opacity must not be denseer (limit 0.0005%).
The inspection method of 5 clarithromycin sulfite salt limit of embodiment, includes the following steps：
(1) precision weighs sodium hydrogensulfite 162.5mg and (is equivalent to the SO containing 100mg2), it sets in 100ml measuring bottles, adds purifying
Water dissolution is simultaneously diluted to scale, shakes up；Precision measures 1ml, sets in 10ml measuring bottles, purified water is added to be diluted to scale, shake up, as
Standard solution of sodium bisulfite (contains SO2A concentration of 100 μ g/ml).
(2) take clarithromycin appropriate, finely ground, precision weighs fine powder 5.0g, adds appropriate amount of water, shake well, filter
It crosses, filtrate is set in 50ml nessler colorimetric tubes, water is added to make into 40ml, add dilute hydrochloric acid 2ml, add 30% hydrogen peroxide 2ml, shake up, i.e.,
For test solution.
(3) standard solution of sodium bisulfite 2ml is taken, is set in 50ml nessler colorimetric tubes, adds water to make into about 40ml, adds dilute hydrochloric acid
2ml adds 30% hydrogen peroxide 2ml, shakes up, as contrast solution.
(4) it is separately added into 25% barium chloride solution 5ml in test solution and contrast solution, is diluted with water to 50ml,
It fully shakes up, places 10 minutes, with setting in black background, from above colorimetric cylinder downwards, compare, what test solution generated
White opacity must not be denseer (limit 0.004%).
The inspection method of 6 injection dexamethasone sulfite salt limit of embodiment, includes the following steps：
(1) precision weighs sodium hydrogensulfite 162.5mg and (is equivalent to the SO containing 100mg2), it sets in 100ml measuring bottles, adds purifying
Water dissolution is simultaneously diluted to scale, shakes up；Precision measures 1ml, sets in 10ml measuring bottles, purified water is added to be diluted to scale, shake up, as
Standard solution of sodium bisulfite (contains SO2A concentration of 100 μ g/ml).
(2) precision weighs injection dexamethasone freeze-dried powder 5.0g, sets in 50ml nessler colorimetric tubes, is dissolved in water and makes
At 40ml, add dilute hydrochloric acid 2ml, adds 30% hydrogen peroxide 2ml, shake up, as test solution.
(3) standard solution of sodium bisulfite 2ml is taken, is set in 50ml nessler colorimetric tubes, adds water to make into about 40ml, adds dilute hydrochloric acid
2ml adds 30% hydrogen peroxide 2ml, shakes up, as contrast solution.
(4) it is separately added into 25% barium chloride solution 5ml in test solution and contrast solution, is diluted with water to 50ml,
It fully shakes up, places 10 minutes, with setting in black background, from above colorimetric cylinder downwards, compare, what test solution generated
White opacity must not be denseer (limit 0.004%).
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
Depending on protection scope of the present invention.
Claims (1)
1. a kind of detection method of sulphite limit, which is characterized in that the detection method of the sulphite limit is for detecting
Test solution obtained is with coloured drug in step 3；
Include the following steps：
Step 1, sulphite standard solution is prepared；Wherein, sulphite standard solution is with SO2A concentration of c is counted, unit is μ g/
ml；
Step 2, it is calculated as follows to obtain the value of the drug amount of taking w, unit g：
Wherein：B is to test pre-designed sulphite standard solution to take volume, units/ml；
A is to be detected drug sulfite salt with SO2The weight limit of meter, is indicated with %；
Step 3, test solution A and test solution B is prepared：
Test solution A and test solution B is all made of following manner preparation：
Step 3.1, the value for the drug amount of taking being calculated by step 2, precision weigh drug；
Step 3.2, appropriate amount of water, shake well is added to make it dissolve into drug, it is such as insoluble, it should filter, take filtrate；
Step 3.3, whether the solution that judgment step 3.2 obtains is alkalinity, if it is, dilute hydrochloric acid is added dropwise into solution into
Property；Then step 3.4 is executed；Otherwise, step 3.4 is directly executed；
Step 3.4, it is V1 the solution that step 3.3 obtains to be settled to volume with water；The dilute hydrochloric acid that volume is V2 is added to carry out
Acidification obtains acid solution；
Step 3.5, whether the solution that judgment step 3.4 obtains is clear solution, if it is not, then filtration step 3.4 obtain it is molten
Liquid obtains clear solution；Then step 3.6 is executed；Otherwise, step 3.6 is directly executed；
Step 3.6, whether the clear solution that judgment step 3.5 obtains carries color, if so, thening follow the steps 3.7；
Step 3.7, the hydrogen peroxide of 3%~30% mass fraction, the body that hydrogen peroxide is added are added dropwise in the solution obtained to step 3.5
Product is V3, is shaken up, and is sulfate by the sulphite complete oxidation in acid solution by the way that hydrogen peroxide is added, so far matches and be made
To final test solution；
Step 4, contrast solution is prepared：
Step 4.1, excessive barium chloride solution is added into test solution A, fully shakes up and stands, judges whether solution shows
Muddiness, if it is, repeated filtration, until obtaining clear filtrate；
Step 4.2, by the value of b used by step 2, the step 1 that precision measures corresponding volume prepares obtained sulphite mark
Quasi- solution；And the sulphite standard solution of measurement is added in the clear filtrate that step 4.1 obtains；
Step 4.3, the hydrogen peroxide of 3%~30% mass fraction is added dropwise in the acid solution obtained to step 4.2, hydrogen peroxide is added
Volume be V3, shake up, so far prepare obtain final contrast solution；
Step 5, the contrast solution that the test solution B and step 4 that step 3 obtains are obtained is respectively placed in No. 1 colorimetric cylinder and No. 2 ratios
In colour tube；Then, it is separately added into excessive barium chloride solution into test solution B and contrast solution, then uses water constant volume respectively
It is V4 to volume, fully shakes up, stands 0~120 minute；Ocular estimate observes whether the muddiness that test solution generates is less than control
The muddiness that product solution generates；If it is, the content of detected drug sulfite salt is less than the value of weight limit a, it is detected
The drug of survey meets the requirements；Otherwise, the content of detected drug sulfite salt is higher than the value of weight limit a, detected
Drug is undesirable.
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| CN107589112A (en) * | 2017-09-11 | 2018-01-16 | 南京御匾国健生物科技有限公司 | A kind of sulphite detection reagent and its detection method |
| CN109765087B (en) * | 2019-01-17 | 2021-12-28 | 广西科技大学 | Method for rapidly extracting and detecting malachite green in freshwater fish |
| CN112255224B (en) * | 2020-11-30 | 2022-08-09 | 郑州原理生物科技有限公司 | Method for detecting signal impurity sulfate ion in acridine compound |
| CN112881373B (en) * | 2021-01-11 | 2023-12-01 | 杭州华东医药集团新药研究院有限公司 | Method for detecting residual quantity of sulfate in oxaagoli sodium |
| CN113567424B (en) * | 2021-07-27 | 2023-10-24 | 西安乐析医疗科技有限公司 | Inspection method for controlling magnesium salt limit in balanced salt solution raw material calcium chloride |
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