CN104133012B - Method for measuring asenapine maleate racemate by high performance liquid chromatography - Google Patents
Method for measuring asenapine maleate racemate by high performance liquid chromatography Download PDFInfo
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- CN104133012B CN104133012B CN201410310045.9A CN201410310045A CN104133012B CN 104133012 B CN104133012 B CN 104133012B CN 201410310045 A CN201410310045 A CN 201410310045A CN 104133012 B CN104133012 B CN 104133012B
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Abstract
The invention belongs to the field of analytical chemistry, and discloses a method for separating and analyzing asenapine maleate and racemate thereof by using a liquid chromatography. The method has the advantages of strong specificity, high accuracy and simple and convenient operation.
Description
Technical Field
The invention discloses an HPLC method, and particularly relates to an analytical separation method of asenapine maleate and a racemate thereof.
Background
Asenapine maleate is used for acute mania or type I bipolar disorder with/without psychotic disorders. Asenapine, developed by merck and oganong biotechnology, is a novel atypical antipsychotic discovered by structural modification of the tetracyclic antidepressant, mianserin. It is a racemic mixture and has dual antagonistic effects on the 52HT2 and D2 receptors. The chemical name of the maleic acid asenapine is (3aRS, 12bRS) -5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1Hdibenz [2,3:6,7 ]]oxepino[4,5-c]Pyrrole (2Z) -2-buteledate (1:1) with molecular formula C21H20ClNO5. The structural formula of the asenapine maleate is as follows:
the racemic structural formula of the compound is as follows:
the method for analyzing and separating the asenapine maleate and the racemate thereof has important practical significance for synthesizing the asenapine maleate raw material medicine and controlling the quality of optical impurities in the asenapine maleate raw material medicine.
Disclosure of Invention
The invention aims to provide a high-efficiency liquid phase method for analyzing and separating asenapine maleate and raceme thereof, thereby ensuring the accuracy of purity detection of the asenapine maleate and realizing the quality control of the final product raw material medicine.
The method for analyzing the purity of asenapine maleate and separating the racemate thereof by using the high performance liquid chromatography adopts a chiral chromatographic column with amylose-tri- (3, 5-xylyl carbamate) as a filler and n-hexane-lower alcohol solution as a mobile phase.
The chiral chromatographic column adopted by the invention is CHIRALPAK AD or CHIRALPAK AD-H.
The lower alcohol solution used in the invention is selected from methanol, absolute ethyl alcohol, propyl alcohol and isopropyl alcohol, and preferably absolute ethyl alcohol and isopropyl alcohol.
The volume ratio of the mobile phase lower alcohol to the n-hexane system is 40: 60-0: 100, and the preferable ratio is 10: 90-0: 100.
The invention adds 0.1% diethylamine into the mobile phase.
The analysis and separation method can be realized according to the following method:
(1) taking proper amount of each asenapine maleate and racemate thereof, respectively dissolving a sample by using absolute ethyl alcohol, and preparing a sample solution containing 0.05-1 mg/mL, preferably 0.5mg/mL of asenapine maleate and racemate thereof;
(2) setting the flow rate of a mobile phase to be 0.4-1.0 mL/min, preferably 0.5mL/min, the detection wavelength to be 200-230 nm, preferably 210nm, and the column temperature to be room temperature;
(3) and (2) injecting 10-50 mu L, preferably 10 mu L of the sample solution in the step (1) into a liquid chromatograph to complete the separation and analysis of the asenapine maleate and the racemate thereof.
The instrument and the optimal chromatographic conditions used by the invention are as follows:
high performance liquid chromatograph: shimadzu: LC-10ATvp, SPD-M10Avp
A chromatographic column: AD-H (CHIRALPAK 250mm x 4.6mm)
Mobile phase: n-Hexane-Isopropanol =93:7, 0.1% diethylamine was added
Flow rate: 0.5mL/min
Detection wavelength: 210nm
Column temperature: at room temperature
Sample introduction volume: 10 μ L.
The invention adopts AD-H (CHIRALPAK, 250mm x 4.6mm), can effectively separate the asenapine maleate and the raceme thereof, and accurately measure the purity of the asenapine maleate and the raceme thereof; the method solves the problem of separation and analysis of the asenapine maleate and the racemate thereof, thereby ensuring the controllable quality of the asenapine maleate intermediate raw material medicine (the result is shown in the attached figures 1-7).
Drawings
FIG. 1 is an HPLC chromatogram of asenapine maleate racemate in example 1;
FIG. 2 is an asenapine maleate HPLC chromatogram of example 1;
FIG. 3 is an HPLC chromatogram of asenapine maleate racemate in example 2;
FIG. 4 is an HPLC chromatogram of asenapine maleate in example 2;
FIG. 5 is a solvent HPLC chromatogram for example 3;
FIG. 6 is an HPLC chromatogram of asenapine maleate racemate in example 3;
FIG. 7 is an HPLC chromatogram of asenapine maleate in example 3.
Detailed Description
Example 1
Instruments and conditions:
high performance liquid chromatograph: shimadzu: LC-10ATvp, SPD-M10 Avp;
a chromatographic column: AD-H (CHIRALPAK, 250mm 4.6 mm);
mobile phase: n-hexane-isopropanol =90:10
Flow rate: 0.5 mL/min;
detection wavelength: 220 nm;
column temperature: room temperature;
sample introduction volume: 10 μ L.
Experimental procedure
Taking proper amount of asenapine maleate and racemate thereof, respectively dissolving samples by using absolute ethyl alcohol to prepare sample solution containing about 0.5mg/mL of asenapine maleate and racemate thereof, taking proper amount of absolute ethyl alcohol as a blank solvent, carrying out high performance liquid chromatography analysis according to the conditions, and recording chromatogram, wherein the result is shown in figure 1 ~ 2, figure 1 is HPLC chromatogram of asenapine maleate racemate, figure 2 is HPLC chromatogram of asenapine maleate, and the result shows that the asenapine maleate and optical isomers can not be completely separated under the conditions, and the peak time of the asenapine maleate is 14.550 min.
Example 2
Instruments and conditions:
high performance liquid chromatograph: shimadzu: LC-10ATvp, SPD-M10Avp
A chromatographic column: AD-H (CHIRALPAK, 250mm 4.6mm)
Mobile phase: n-hexane-isopropanol =95:5, 0.005% diethylamine was added
Flow rate: 0.5mL/min
Detection wavelength: 210nm
Column temperature: at room temperature
Sample introduction volume: 10 μ L.
Experimental procedure
Taking a proper amount of asenapine maleate and a proper amount of ananas maleate racemate, respectively dissolving samples by using absolute ethyl alcohol to prepare a sample solution containing about 0.5mg/mL of asenapine maleate and the ananas maleate, carrying out high performance liquid chromatography analysis according to the conditions, recording chromatograms, and obtaining results shown in figure 3 ~ 4, figure 3 is an HPLC chromatogram of the asenapine maleate racemate, figure 4 is the HPLC chromatogram of the asenapine maleate, so that the asenapine maleate and optical isomers thereof cannot achieve baseline separation under the conditions, the chromatographic peak tailing is serious, and the peak time of the asenapine maleate is 19.550 min.
Example 3
Instruments and conditions:
high performance liquid chromatograph: shimadzu: LC-10ATvp, SPD-M10Avp
A chromatographic column: AD-H (CHIRALPAK 250mm x 4.6mm)
Mobile phase: n-Hexane-Isopropanol =93:7, 0.1% diethylamine was added
Flow rate: 0.5mL/min
Detection wavelength: 210nm
Column temperature: at room temperature
Sample introduction volume: 10 μ L.
Experimental procedure
Taking proper amount of asenapine maleate and racemate thereof, respectively dissolving samples with absolute ethyl alcohol to prepare sample solutions containing about 0.5mg/mL of asenapine maleate and racemate thereof, carrying out high performance liquid chromatography analysis according to the conditions, and recording chromatograms, wherein the result is shown in figure 5 ~ 7, figure 5 is an HPLC chromatogram of absolute ethyl alcohol as a solvent, figure 6 is an HPLC chromatogram of asenapine maleate racemate, and figure 7 is an HPLC chromatogram of asenapine maleate, so that the asenapine maleate and optical isomers can be completely separated under the conditions, and the peak time of the asenapine maleate is 15.614 min.
Claims (1)
1. A method for separating asenapine maleate racemate by high performance liquid chromatography is characterized in that: adopting CHIRALPAKAD-H, a chiral chromatographic column with the model of 250mmL multiplied by 4.6mmD, wherein the mobile phase is n-hexane and isopropanol, the volume ratio is 93:7, 0.1% diethylamine is added into the mobile phase, the flow rate is 0.5mL/min, the detection wavelength is 210nm, the column temperature is room temperature, taking a proper amount of an asenapine maleate racemate sample, dissolving the sample with absolute ethyl alcohol to prepare a sample solution containing 0.05-1 mg of asenapine maleate racemate per 1mL, and injecting 10-50 mu L of the sample solution into a liquid chromatograph to complete the analysis and separation of the asenapine maleate and the optical isomer thereof.
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112019012573A2 (en) | 2016-12-20 | 2019-11-19 | Lts Lohmann Therapie Systeme Ag | transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene |
| EP3338768B1 (en) | 2016-12-20 | 2019-10-30 | LTS Lohmann Therapie-Systeme AG | Transdermal therapeutic system containing asenapine |
| WO2019002204A1 (en) | 2017-06-26 | 2019-01-03 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine and silicone acrylic hybrid polymer |
| BR112020026099A2 (en) | 2018-06-20 | 2021-03-23 | Lts Lohmann Therapie-Systeme Ag | transdermal therapeutic system containing asenapine |
| 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3992547A (en) * | 1974-11-20 | 1976-11-16 | Merck & Co., Inc. | 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine-N-oxide isomer |
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| EP1948637A4 (en) * | 2005-11-14 | 2010-09-08 | Hetero Drugs Ltd | Process for amorphous esomeprazole |
| CA2741928A1 (en) * | 2008-11-03 | 2010-06-03 | Generics [Uk] Limited | Hplc method for the analysis of bosentan and related substances and use of these substances as reference standards and markers |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3992547A (en) * | 1974-11-20 | 1976-11-16 | Merck & Co., Inc. | 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine-N-oxide isomer |
Non-Patent Citations (2)
| Title |
|---|
| High throughput identification and quantification of 16 antipsychotics and 8 major metabolites in serum using ultra-high performance liquid chromatography–tandem mass spectrometry;Lisbeth Patteet等;《Clinica Chimica Acta》;20140228;第429卷;全文 * |
| STRESS DEGRADATION STUDIES AND DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE ESTIMATION OF ASENAPINE MALEATE;ANEESH T.P等;《International Journal of Pharmacy and Pharmaceutical Sciences》;20120430;第4卷(第4期);第448-451页 * |
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Address after: 102206 south building, Boda building, Life Science Park, Changping District, Beijing (Wanquan) Patentee after: BEIJING VENTUREPHARM BIOTECH Corp. Address before: 102206 Beijing City, Changping District Zhongguancun Life Science Park building, Boda Wanquan (Beijing) innovation base Patentee before: BEIJING VENTUREPHARM BIOTECH Corp. |