Determination of asenapine in presence of its inactive metabolites in human plasma by LC-MS/MS

作     者：Nirav R Patel Mallika Sanyal Naveen Sharma Dinesh S.Patel Pranav S.Shrivastav Bhavin N.Patel 

作者机构：Bioanalytical LaboratoryUiantha Research India Ltd.BodakdevAhmedabad 380054GujaratIndia Kadi Sarva ViswavidyalayaSector-15Ghandhinagar 382715GujaratIndia Department of ChemistrySt.Xavier's CollegeNavrangpuraAhmedabad 380009GujaratIndia Department of ChemistrySchool of SciencesGujarat UniversityNavrangpuraAhmedabad 380009GujaratIndia 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2018年第8卷第5期

页      面：341-347页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 09[农学] 070302[理学-分析化学] 0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 090403[农学-农药学(可授农学、理学学位）] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0904[农学-植物保护] 0703[理学-化学] 0702[理学-物理学] 

主　　题：Asenapine Asenapine 13C-d3 Metabolites LC-MS/MS Bioequivalence study Human plasma 

摘      要：A highly selective and sensitive liquid chromatography-tandem mass spectrometry （LC-MS/MS） assay has been described for the determination of asenapine （ASE） in presence of its inactive metabolites N-desmethyl asenapine （DMA） and asenapine-N-glucuronide （ASG）. ASE, and ASE 13C-d3, used as internal standard （IS）, were extracted from 300 μL human plasma by a simple and precise liquid-liquid extraction procedure using methyl tert-butyl ether. Baseline separation of ASE from its inactive metabolites was achieved on Chromolith Performance RPse （100 mm ×4.6 mm） column using acetonitrile- 5.0 mM ammonium acetate-10% formic acid （90：10：0.1, v/v/v） within 4.5 min. Quantitation of ASE was done on a triple quadrupole mass spectrometer equipped with electrospray ionization in the positive mode. The protonated precursor to product ion transitions monitored for ASE and ASE 13C-d3 were m/z 286.1 → 166.0 and m/z 290.0 → 166.1, respectively. The limit of detection （LOD） and limit of quantitation （LOQ） of the method were 0.0025 ng/mL and 0.050 ng/mL respectively in a linear concentration range of 0.050-20.0 ng/mL for ASE. The intra-batch and inter-batch precision （% CV） and mean relative recovery across quality control levels were 〈 5.8% and 87.3%, respectively. Matrix effect, evaluated as IS-normalized matrix factor, ranged from 1.03 to 1.05. The stability of ASE under different storage conditions was ascertained in presence of the metabolites. The developed method is much simpler, matrix free, rapid and economical compared to the existing methods. The method was suc- cessfully used for a bioequivalence study of asenapine in healthy Indian subjects for the first time.