CN105974036A - Detection method of aminopyridine isomer - Google Patents
Detection method of aminopyridine isomer Download PDFInfo
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- CN105974036A CN105974036A CN201610612294.2A CN201610612294A CN105974036A CN 105974036 A CN105974036 A CN 105974036A CN 201610612294 A CN201610612294 A CN 201610612294A CN 105974036 A CN105974036 A CN 105974036A
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- China
- Prior art keywords
- solution
- high performance
- performance liquid
- flowing
- gelieting
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Classifications
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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
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
Abstract
The invention discloses a detection method of an aminopyridine isomer. The method is implemented by adopting a high performance liquid chromatography. The method comprises the following steps that 1, a starting material sample solution is prepared; 2, the sample solution obtained in the step 1 is injected into a high performance liquid chromatograph, a flowing phase is adopted for isocratic elution, and a chromatogram map is recorded, wherein amylose-tris(3,5-dimethylphenylcarbamate) is used as a filling agent according to a chromatographic column fixing phase of the high performance liquid chromatography, and n-heptane-isopropanol-diethylamine (90:10:0.05) is adopted as the flowing phase. The detection method detects starting material isomers under the same liquid phase condition and is strong in specificity, and detection results are accurate and dependable.
Description
Technical field
The present invention relates to drug measurement techniques field, be specifically related to the detection method of a kind of aminopyridine isomer.
Background technology
Li Gelieting (Linagliptin Tablets), Li Gelieting are a kind of dipeptidyl peptidase-4 (DPP-4) suppression
Agent, can improve the different blood glucose levels of type 2 diabetes mellitus (T2DM) adult patients on the basis of diet control and physical training.Phase
Prepare and raw material is commonly used S-(R)-3-t-butoxycarbonyl amino piperidines, but it has multiple isomer, the most very
Good detection method.
Summary of the invention
The technical problem to be solved in the present invention is the defect overcoming prior art, it is provided that the inspection of a kind of aminopyridine isomer
Survey method.
In order to solve above-mentioned technical problem, the invention provides following technical scheme: a kind of aminopyridine isomer
Detection method, the method uses high performance liquid chromatography to carry out, its
Comprise the steps:
(1) preparation Li Gelieting initiation material sample solution, described Li Gelieting initiation material sample solution includes that test sample is molten
Liquid；And reference substance solution；
(2) step (1) gained sample solution is injected high performance liquid chromatograph, use flowing to carry out gradient mutually as flowing and wash
De-, and record chromatogram；
Wherein, the preparation method of described need testing solution comprises the steps: that precision weighs Li Gelieting initiation material, adds dilution
Liquid dissolves and is diluted to the concentration of Li Gelieting is 10mg/ml, obtains need testing solution；
The chromatographic column fixed phase amylose-three (3,5-xylyl carbamate) of described high performance liquid chromatography is for filling out
Fill agent；
Flowing phase: normal heptane-isopropanol-diethylamine (90: 10: 0.05).
Preferably, the volume being formulated as normal heptane of described flowing phase: isopropanol: volume=90 of diethylamine solution: 10:
0.05。
Preferably, the gradient elution order of described high performance liquid chromatography is as follows:
When 0-20 minute, flowing is mutually: 100 volume %.
Preferably, the flow velocity of described flowing phase is 1.0ml/min.
Preferably, the chromatographic column column temperature of described high performance liquid chromatography is 25～40 DEG C, and detection wavelength is 225nm.
Preferably, described Li Gelieting initiation material sample solution also includes reference substance solution；Take Li Gelietingyue 50mg
With S-t-butoxycarbonyl amino piperidines reference substance about 5mg, add flowing phase 5ml and dissolve, obtain reference substance solution；Described reference substance is molten
The concentration of liquid is 10mg/ml.
Preferably, in described Li Gelieting initiation material need testing solution, the concentration of initiation material is 10mg/ml.
Preferably, in step (2), first sample controls solution is injected chromatograph of liquid, regulates detector sensitivity,
Make peak height is monitor full scale the 80% of main constituent chromatographic peak；Again need testing solution and reference substance solution are injected separately into liquid
Chromatography, uses flowing to carry out isocratic elution mutually, and records chromatogram；Preferably, sample solution in chromatograph of liquid is injected
Amount be 10 μ l.
Preferably, the chromatographic column column temperature of described high performance liquid chromatography is 30 DEG C.
Detection method measures under same liquid-phase condition that initiation material isomer assay method specificity is strong, detection
Result is the most credible.
Embodiment
Using high performance liquid chromatography to carry out, step includes:
(1) preparation Li Gelieting initiation material sample solution, described Li Gelieting initiation material sample solution includes that test sample is molten
Liquid；And reference substance solution；
(2) step (1) gained sample solution is injected high performance liquid chromatograph, use flowing to carry out gradient mutually as flowing and wash
De-, and record chromatogram；
Wherein, the preparation method of described need testing solution comprises the steps: that precision weighs Li Gelieting initiation material, adds dilution
Liquid dissolves and is diluted to the concentration of Li Gelieting is 10mg/ml, obtains need testing solution；
The chromatographic column fixed phase amylose-three (3,5-xylyl carbamate) of described high performance liquid chromatography is for filling out
Fill agent；
Flowing phase: normal heptane-isopropanol-diethylamine (90: 10: 0.05).
Chromatographic condition:
Chromatographic column: Chiralpak AD-H 5um, 25cm × 4.6mm
Flow velocity: 1.0ml/min detects wavelength: 225nm
Sample size: 10ul column temperature: 30 DEG C
Flowing phase: normal heptane-isopropanol-diethylamine (90:10:0.05)
Sample preparation:
Test sample: take this product appropriate, with flowing phased soln and quantitatively dilution make the sample that every 1ml contains 10mg.
Reference substance: take this product about 50mg, compares pale blue 5mg with S-t-butylcarbonylamino piperidines, adds flowing phase 5ml molten
Solve.
Algoscopy:
Taking reference substance 10ul and inject chromatograph of liquid, S isomer peak should meet the requirements with the separating degree of main peak.Take need testing solution
10ul injects chromatograph of liquid, records chromatogram, is only integrated S isomer peak with main peak.In need testing solution chromatogram,
Calculating by area normalization method, S isomer must not cross 0.2%.
Claims (9)
1. a detection method for aminopyridine isomer, described initiation material isomer includes S-(R)-3-tertbutyloxycarbonyl ammonia
Phenylpiperidines, the method uses high performance liquid chromatography to carry out, it is characterised in that comprise the steps:
(1) preparation Li Gelieting initiation material sample solution, described Li Gelieting initiation material sample solution includes that test sample is molten
Liquid；And reference substance solution；
(2) step (1) gained sample solution is injected high performance liquid chromatograph, use flowing to carry out gradient mutually as flowing and wash
De-, and record chromatogram；
Wherein, the preparation method of described need testing solution comprises the steps: that precision weighs Li Gelieting initiation material, adds dilution
Liquid dissolves and is diluted to the concentration of Li Gelieting is 10mg/ml, obtains need testing solution；
The chromatographic column fixed phase amylose-three (3,5-xylyl carbamate) of described high performance liquid chromatography is for filling out
Fill agent；
Flowing phase: normal heptane-isopropanol-diethylamine (90: 10: 0.05).
Method the most according to claim 1, it is characterised in that the volume being formulated as normal heptane of described flowing phase: isopropyl
Alcohol: volume=90 of diethylamine solution: 10: 0.05.
Method the most according to claim 1, it is characterised in that the gradient of described high performance liquid chromatography is washed
De-order is as follows:
When 0-20 minute, flowing is mutually: 100 volume %.
Method the most according to claim 1, it is characterised in that the flow velocity of described flowing phase is 1.0ml/min.
Method the most according to claim 1, it is characterised in that the chromatographic column column temperature of described high performance liquid chromatography is 25
～40 DEG C, detection wavelength is 225nm.
Method the most according to claim 1, it is characterised in that it is right that described Li Gelieting initiation material sample solution also includes
According to product solution；Take Li Gelietingyue 50mg and S-t-butoxycarbonyl amino piperidines reference substance about 5mg, add flowing phase 5ml and dissolve, i.e.
Obtain reference substance solution；The concentration of described reference substance solution is 10mg/ml.
Method the most according to claim 1, it is characterised in that initial in described Li Gelieting initiation material need testing solution
The concentration of raw material is 10mg/ml.
Method the most according to claim 1, it is characterised in that in step (2), first injects liquid by sample controls solution
Chromatography, regulates detector sensitivity, makes peak height is monitor full scale the 80% of main constituent chromatographic peak；Again by test sample
Solution and reference substance solution are injected separately into chromatograph of liquid, use flowing to carry out isocratic elution mutually, and record chromatogram；Preferably
Ground, the amount of sample solution in chromatograph of liquid of injecting is 10 μ l.
Method the most according to claim 5, it is characterised in that the chromatographic column column temperature of described high performance liquid chromatography is 30
℃。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610612294.2A CN105974036A (en) | 2016-07-31 | 2016-07-31 | Detection method of aminopyridine isomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610612294.2A CN105974036A (en) | 2016-07-31 | 2016-07-31 | Detection method of aminopyridine isomer |
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| CN105974036A true CN105974036A (en) | 2016-09-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610612294.2A Pending CN105974036A (en) | 2016-07-31 | 2016-07-31 | Detection method of aminopyridine isomer |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114324663A (en) * | 2021-12-31 | 2022-04-12 | 北京金城泰尔制药有限公司 | Method for detecting lornoxicam related substances |
| CN114354801A (en) * | 2021-12-31 | 2022-04-15 | 山东大学 | Method for analyzing content of three aminopyridine isomers in (R) -3-Boc-aminopiperidine |
| CN115856102A (en) * | 2021-09-23 | 2023-03-28 | 江苏正大清江制药有限公司 | (R) -3-Boc-aminopiperidine quality control method |
Citations (3)
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| CN102203075A (en) * | 2008-09-02 | 2011-09-28 | 诺瓦提斯公司 | Bicyclic kinase inhibitors |
| CN105734089A (en) * | 2014-12-11 | 2016-07-06 | 南京博优康远生物医药科技有限公司 | An asymmetric synthesis method for (R)-3-amino piperidine derivatives |
| CN105753771A (en) * | 2014-12-20 | 2016-07-13 | 无锡乾浩生物医药有限公司 | A synthetic method of a medical intermediate trans-3-N-boc-aminopiperidine |
-
2016
- 2016-07-31 CN CN201610612294.2A patent/CN105974036A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102203075A (en) * | 2008-09-02 | 2011-09-28 | 诺瓦提斯公司 | Bicyclic kinase inhibitors |
| CN105734089A (en) * | 2014-12-11 | 2016-07-06 | 南京博优康远生物医药科技有限公司 | An asymmetric synthesis method for (R)-3-amino piperidine derivatives |
| CN105753771A (en) * | 2014-12-20 | 2016-07-13 | 无锡乾浩生物医药有限公司 | A synthetic method of a medical intermediate trans-3-N-boc-aminopiperidine |
Non-Patent Citations (2)
| Title |
|---|
| HEIKO SCHRAMM ET AL: "Synthesis of Triazolyl-Substituted 3-Aminopiperidines by Huisgen-1,3-Dipolar Cycloaddition – New Scaffolds for Combinatorial Chemistry", 《EUROPEAN JOURNAL OF ORGANIC CHEMISTRY》 * |
| 孙成钰 等: "利拉利汀合成路线图解", 《中国新药杂志》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115856102A (en) * | 2021-09-23 | 2023-03-28 | 江苏正大清江制药有限公司 | (R) -3-Boc-aminopiperidine quality control method |
| CN115856102B (en) * | 2021-09-23 | 2023-11-10 | 江苏正大清江制药有限公司 | Quality control method of (R) -3-Boc-aminopiperidine |
| CN114324663A (en) * | 2021-12-31 | 2022-04-12 | 北京金城泰尔制药有限公司 | Method for detecting lornoxicam related substances |
| CN114354801A (en) * | 2021-12-31 | 2022-04-15 | 山东大学 | Method for analyzing content of three aminopyridine isomers in (R) -3-Boc-aminopiperidine |
| CN114324663B (en) * | 2021-12-31 | 2023-08-15 | 北京金城泰尔制药有限公司 | Method for detecting lornoxicam-related substances |
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