CN111983075A - Method for detecting rasagiline and enantiomer thereof - Google Patents
Method for detecting rasagiline and enantiomer thereof Download PDFInfo
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- CN111983075A CN111983075A CN202010824458.4A CN202010824458A CN111983075A CN 111983075 A CN111983075 A CN 111983075A CN 202010824458 A CN202010824458 A CN 202010824458A CN 111983075 A CN111983075 A CN 111983075A
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- G—PHYSICS
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- 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
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Abstract
The invention discloses a method for separating and detecting rasagiline and enantiomers thereof, which comprises the steps of using a chromatographic column with 3, 5-dimethyl benzoate derived amylose bonded silica gel as a filler, carrying out HPLC ultraviolet detection, wherein the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (85-95: 15-5: 0-0.1), the flow rate is 1.0ml/min, and the sample injection amount is 20 mu l.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for detecting rasagiline and an enantiomer thereof.
Background
Rasagiline mesylate is an irreversible and selective monoamine oxidase inhibitor, monoamine oxidase is an enzyme participating in metabolic degradation of dopamine in brain, and after the enzyme is inhibited, a transfer signal of dopamine is enhanced, so that the rasagiline mesylate is beneficial to Parkinson's disease and can also enhance the action of levodopa, and therefore, the rasagiline mesylate composition is used for treating the Parkinson's disease and can also be used as an auxiliary medicament of the levodopa.
According to the chemical structure of rasagiline mesylate (shown as a compound in the following formula I), the drug contains a chiral center, enantiomer (shown as a compound in the following formula II) impurities can be introduced in the process of synthesizing the drug, and the impurities are highly similar to the rasagiline mesylate in result and cannot be detected by a conventional related substance determination method, so that an impurity detection method with strong specificity needs to be developed to control the impurities, and a related document for determining the impurities is not found at present.
CN201410059002.8 discloses a product quality detection method for rasagiline mesylate raw materials and preparations thereof, which uses HPLC and/or HPLC-MS for detection, and the detection conditions are that the mobile phase: the volume ratio of triethylamine-glacial acetic acid buffer solution to acetonitrile with the pH value of 5.0-6.0 is 40: 60-60: 40, wherein the triethylamine-glacial acetic acid buffer solution with the pH value of 5.0-6.0 consists of triethylamine-glacial acetic acid buffer pairs, 900 parts of water is added with 4 parts of triethylamine, and the pH value is adjusted to 5.0-6.0 by glacial acetic acid; flow rate: 0.8-1.2 mL/min; column temperature: 25-35 ℃; detection wavelength: 210-220 nm. Preferably, the volume ratio of triethylamine-glacial acetic acid buffer solution-acetonitrile of the mobile phase is 50: 50, the flow rate is 1.0mL/min, the column temperature is 30 ℃, and the detection wavelength is 215 nm. However, the method cannot effectively separate and detect rasagiline mesylate from the enantiomer thereof.
Disclosure of Invention
The invention aims to provide a method for detecting rasagiline and an enantiomer thereof, which can conveniently and rapidly detect the enantiomer impurity in rasagiline mesylate and has the advantages of good peak shape (the asymmetry is less than 1.2, the number of theoretical plates is more than 10000), good separation degree of the enantiomer and a main peak (the separation degree is more than 3.0) and the like.
To achieve the object of the present invention, the following embodiments are provided.
The invention relates to a method for separating and detecting rasagiline or salt and enantiomer thereof, which comprises the following steps: the detection is carried out by adopting a high performance liquid chromatograph and an ultraviolet detector, wherein 3, 5-dimethylbenzoate derived amylose bonded silica gel is used as a filler in a chromatographic column, and n-hexane-isopropanol-diethylamine is used as a mobile phase, and the volume ratio of the n-hexane-isopropanol-diethylamine to the mobile phase is 85-95: 15-5: 0-0.1).
In the method of the present invention, the volume ratio of the mobile phase n-hexane-isopropanol-diethylamine is 85-95: 15-5: 0.05-0.1, more preferably 85:15: 0.05; the detection wavelength is 272nm, the column temperature is 30 ℃, the flow rate is 1.0ml/min, and the sample injection amount is 20 mul; the chromatographic column has a length of 25cm, a diameter of 4.6mm and a particle size of 5 μm.
In the above method of the present invention, the salt is a methanesulfonate salt.
The method of the present invention further comprises the steps of:
1) weighing appropriate amount of rasagiline or its mesylate and rasagiline enantiomer, respectively, adding mobile phase (n-hexane-isopropanol-diethylamine or n-hexane-isopropanol) to dissolve, and making into solution containing 0.5mg per 1ml, respectively as control solution;
2) weighing a proper amount of rasagiline or a mesylate sample thereof, adding a mobile phase (n-hexane-isopropanol-diethylamine or n-hexane-isopropanol) for dissolving, and preparing a solution containing about 0.5mg in each 1ml as a test solution;
3) injecting the reference solution and the test solution into the chromatographic column.
The method of the invention has the following effects:
the method can conveniently and rapidly detect the enantiomer impurities in the rasagiline mesylate, and has the advantages of good peaked form (the asymmetry degree is less than 1.2, the number of theoretical plates is more than 10000), good separation degree of the enantiomer from a main peak (the separation degree is more than 3.0) and the like.
Drawings
FIG. 1 is an HPLC chromatogram of example 1;
FIG. 2 is an HPLC chromatogram of example 2;
FIG. 3 is an HPLC chromatogram of example 3;
FIG. 4 is an HPLC chromatogram of example 4;
FIG. 5 is an HPLC chromatogram of example 5;
FIG. 6 is an HPLC chromatogram of example 6;
FIG. 7 is an HPLC chromatogram of example 7.
Detailed Description
The following examples are merely representative for further illustration and understanding of the spirit of the present invention. But not to limit the scope of the invention in this regard.
Example 1
An Agilent 1260 high performance liquid chromatograph and an ultraviolet detector are used, a chromatographic column (CHIRALCEL OD) with 3, 5-dimethyl benzoate derived cellulose bonded silica gel as a filler is used, the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (90:10:0, volume ratio, the same below), the flow rate is 1.0ml/min, and the sample injection amount is 20 mul. Taking 10mg of each rasagiline mesylate reference substance and rasagiline enantiomer reference substance, precisely weighing, placing in a 100ml measuring flask, adding n-hexane-isopropanol (90:10, volume ratio, the same below) to dissolve and dilute to scale, shaking up, and taking as a test solution. The test solution was injected into the column, and the results are shown in FIG. 1.
As can be seen from FIG. 1, the 1 st peak from left to right in FIG. 1 is rasagiline enantiomer, the 2 nd peak is rasagiline, the two peaks are not separated effectively, the separation degree is not up to 3.0, and the experimental effect is not achieved.
Example 2
An Agilent 1260 high performance liquid chromatograph and an ultraviolet detector are used, a chromatographic column (CHIRALCEL AD) with 3, 5-dimethylbenzoate derived amylose bonded silica gel as a filler is used, the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (90:10:0), the flow rate is 1.0ml/min, and the sample injection amount is 20 mul. Taking 10mg of each rasagiline mesylate reference substance and rasagiline enantiomer reference substance, precisely weighing, placing in a 100ml measuring flask, adding n-hexane-isopropanol (90:10) to dissolve and dilute to scale, shaking up to obtain reference substance solution. The control solution was injected into the column and the results are shown in FIG. 2.
As can be seen from fig. 2, the two peaks are clearly separated, and although the separation degree of the two peaks is greater than 3.0, the peaks are tailing, and the asymmetry degree is greater than 1.2.
Example 3
An Agilent 1260 high performance liquid chromatograph and an ultraviolet detector are used, a chromatographic column (CHIRALCELAD) with 3, 5-dimethylbenzoate derived amylose bonded silica gel as a filler is used, the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (90:10:0.1), the flow rate is 1.0ml/min, and the sample injection amount is 20 mul. Taking 10mg of each rasagiline mesylate reference substance and rasagiline enantiomer reference substance, precisely weighing, placing in a 100ml measuring flask, adding n-hexane-isopropanol-diethylamine (90:10:0.1) to dissolve and dilute to scale, shaking up to obtain a reference substance solution. The control solution was injected into the column and the results are shown in FIG. 3.
As can be seen from FIG. 3, after 0.1% diethylamine was added to the mobile phase, the peak pattern was significantly improved, and the separation degree of the two peaks was greater than 3.0, which met the requirements, but the peak height was relatively low.
Example 4
An Agilent 1260 high performance liquid chromatograph and an ultraviolet detector are used, a chromatographic column (CHIRALCELAD) with 3, 5-dimethylbenzoate derived amylose bonded silica gel as a filler is used, the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (90:10:0.05), the flow rate is 1.0ml/min, and the sample injection amount is 20 mul. Taking 10mg of each rasagiline mesylate reference substance and rasagiline enantiomer reference substance, precisely weighing, placing in a 100ml measuring flask, adding n-hexane-isopropanol (90:10) to dissolve and dilute to scale, shaking up to obtain reference substance solution. The control solution was injected into the column and the results are shown in FIG. 4.
As can be seen from FIG. 4, after the amount of diethylamine in the mobile phase is reduced from 0.1% to 0.05%, the asymmetry of the two peaks is still less than 1.2, and the separation degree of the two peaks is greater than 3.0, which is satisfactory, but the peak height is relatively low.
Example 5
An Agilent 1260 high performance liquid chromatograph and an ultraviolet detector are used, a chromatographic column (CHIRALCELAD) with 3, 5-dimethylbenzoate derived amylose bonded silica gel as a filler is used, the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (95:5:0.05), the flow rate is 1.0ml/min, and the sample injection amount is 20 mul. Taking 10mg of each rasagiline mesylate reference substance and rasagiline enantiomer reference substance, precisely weighing, placing in a 100ml measuring flask, adding n-hexane-isopropanol (90:10) to dissolve and dilute to scale, shaking up, and taking the reference substance. The control solution was injected into the column and the results are shown in FIG. 5.
As can be seen from FIG. 5, when the mobile phase ratio was adjusted from n-hexane-isopropyl alcohol-diethylamine (90:10:0.05) to n-hexane-isopropyl alcohol-diethylamine (95:5:0.05), the asymmetry of the two peaks was still less than 1.2, the separation of the two peaks was more than 3.0, and although satisfactory, the peak was late and the peak height was low.
Example 6
An Agilent 1260 high performance liquid chromatograph and an ultraviolet detector are used, a chromatographic column (CHIRALCELAD) with 3, 5-dimethylbenzoate derived amylose bonded silica gel as a filler is used, the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (the volume ratio is 85:15:0.05), the flow rate is 1.0ml/min, and the sample injection amount is 20 mul. Taking 10mg of each rasagiline mesylate reference substance and rasagiline enantiomer reference substance, precisely weighing, placing in a 100ml measuring flask, adding n-hexane-isopropanol (volume ratio is 90:10) to dissolve and dilute to scale, shaking up, and taking as reference substance solution. The control solution was injected into the column and the results are shown in FIG. 6.
As can be seen from fig. 6, after the volume ratio of the mobile phase is adjusted from n-hexane-isopropanol-diethylamine (90:10:0.05) to n-hexane-isopropanol-diethylamine (85:15:0.05), the asymmetry of the two peaks is still less than 1.2, and the separation degree of the two peaks is greater than 3.0, which is satisfactory, but the condition is that the peak height is the highest and the sensitivity is the best under the same concentration, which is the optimal condition.
Example 7
An Agilent 1260 high performance liquid chromatograph and an ultraviolet detector are used, a chromatographic column (CHIRALCELAD) with 3, 5-dimethylbenzoate derived amylose bonded silica gel as a filler is used, the detection wavelength is 272nm, the column temperature is 30 ℃, the mobile phase is n-hexane-isopropanol-diethylamine (85:15:0.05), the flow rate is 1.0ml/min, and the sample injection amount is 20 mul. A rasagiline mesylate sample of 10mg is precisely weighed and placed in a 100ml measuring flask, dissolved and diluted to scale by adding n-hexane-isopropanol (90:10), and shaken up to be used as a test solution. The test solution was injected into the column, and the results are shown in FIG. 7.
As can be seen from FIG. 7, the product was tested under the optimal conditions, and the results show that no enantiomer was detected in the product, indicating that the sample has good quality.
The above examples are merely exemplary and any simple variations which do not depart from the spirit of the invention are intended to be within the scope of the invention.
Claims (7)
1. A method for separately detecting rasagiline or a salt and an enantiomer thereof comprising: the detection is carried out by adopting a high performance liquid chromatograph and an ultraviolet detector, 3, 5-dimethyl benzoate derived amylose bonded silica gel is used as a filler for a chromatographic column, and n-hexane-isopropanol-diethylamine is used as a mobile phase, wherein the volume ratio of the n-hexane-isopropanol-diethylamine is 85-95: 15-5: 0-0.1.
2. The method of claim 1, wherein the volume ratio of the mobile phase n-hexane-isopropanol-diethylamine is 85-95: 15-5: 0.05-0.1.
3. The method of claim 2, wherein the mobile phase n-hexane-isopropanol-diethylamine is in a volume ratio of 85:15: 0.05.
4. The method according to claim 1 or 2, wherein the detection wavelength is 272nm, the column temperature is 30 ℃, the flow rate is 1.0ml/min, and the sample volume is 20. mu.l.
5. The method of claim 1 or 2, wherein the chromatographic column has a length of 25cm, a diameter of 4.6mm and a particle size of 5 μm.
6. The method of claim 1, wherein the salt is a mesylate salt.
7. The method of claim 1, comprising the steps of:
1) weighing appropriate amount of rasagiline or its mesylate and rasagiline enantiomer reference substances, respectively, adding mobile phase n-hexane-isopropanol-diethylamine or n-hexane-isopropanol to dissolve, and making into solution containing about 0.5mg per 1ml as reference substance solution; or
2) Weighing a proper amount of rasagiline or a mesylate sample thereof, adding a mobile phase n-hexane-isopropanol-diethylamine or n-hexane-isopropanol to dissolve, and preparing a solution containing about 0.5mg in each 1ml as a test solution;
3) injecting the reference solution or the test solution into the chromatographic column.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115494174A (en) * | 2022-09-23 | 2022-12-20 | 南京瑞孚医药科技有限公司 | Method for detecting thiourea in meloxicam by high performance liquid chromatography |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102010353A (en) * | 2010-10-22 | 2011-04-13 | 湖北能特科技股份有限公司 | New method for preparing rasagiline mesylate |
| WO2011095985A2 (en) * | 2010-02-02 | 2011-08-11 | Glenmark Generics Limited | Rasagiline salts and processes for the preparation thereof |
| US20130089610A1 (en) * | 2011-10-10 | 2013-04-11 | Teva Pharmaceutical Industries, Ltd. | R(+)-n-methyl-propargyl-aminoindan |
| CN103864646A (en) * | 2014-02-21 | 2014-06-18 | 常州市第四制药厂有限公司 | Preparation and analysis method of impurity of rasagiline mesylate |
| CN111333517A (en) * | 2018-12-19 | 2020-06-26 | 上海奥博生物医药技术有限公司 | Improved method for preparing rasagiline |
-
2020
- 2020-08-17 CN CN202010824458.4A patent/CN111983075A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011095985A2 (en) * | 2010-02-02 | 2011-08-11 | Glenmark Generics Limited | Rasagiline salts and processes for the preparation thereof |
| CN102010353A (en) * | 2010-10-22 | 2011-04-13 | 湖北能特科技股份有限公司 | New method for preparing rasagiline mesylate |
| US20130089610A1 (en) * | 2011-10-10 | 2013-04-11 | Teva Pharmaceutical Industries, Ltd. | R(+)-n-methyl-propargyl-aminoindan |
| CN103864646A (en) * | 2014-02-21 | 2014-06-18 | 常州市第四制药厂有限公司 | Preparation and analysis method of impurity of rasagiline mesylate |
| CN111333517A (en) * | 2018-12-19 | 2020-06-26 | 上海奥博生物医药技术有限公司 | Improved method for preparing rasagiline |
Non-Patent Citations (10)
| Title |
|---|
| K.M.TAK等: "Liquid chromatographic resolution of racemic rasagiline and its analogues on a chiral stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid", 《JOURNAL OF SEPARATION SCIENCE》 * |
| N.BALAJI等: "Reversed-Phase UHPLC Enantiomeric Separation of Rasagiline Salts Using a Chiralpak (R) AGP Column", 《SCIENTIA PHARMACEUTICA》 * |
| P.S.REDDY等: "A Validated Normal Phase LC Method for Enantiomeric Separation of Rasagiline Mesylate and Its (S)-Enantiomer on Cellulose Derivative-Based Chiral Stationary Phase", 《CHIRALITY》 * |
| Z.I.SZABO等: "Chiral separation of rasagiline using sulfobutylether-beta-cyclodextrin: capillary electrophoresis, NMR and molecular modeling study", 《ELECTROPHORESIS》 * |
| 周敏等: "HPLC法测定甲磺酸雷沙吉兰片的有关物质", 《上海医药》 * |
| 唐家邓等: "甲磺酸雷沙吉兰的合成", 《中国医药工业杂志》 * |
| 张小洁等: "甲磺酸雷沙吉兰含量测定的方法学研究", 《宜春学院学报》 * |
| 戴荣华等: "雷沙吉兰甲磺酸盐的合成工艺研究", 《中国现代应用药学》 * |
| 杨鹏等: "抗帕金森病新药雷莎吉兰的合成", 《中国新药杂志》 * |
| 郭舜民等: "抗帕金森新药雷莎吉兰的手性合成", 《中国新药杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115494174A (en) * | 2022-09-23 | 2022-12-20 | 南京瑞孚医药科技有限公司 | Method for detecting thiourea in meloxicam by high performance liquid chromatography |
| CN115494174B (en) * | 2022-09-23 | 2024-03-29 | 南京瑞孚医药科技有限公司 | Method for detecting thiourea in meloxicam by high performance liquid chromatography |
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