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Enantioselective LC‐MS/MS method for the determination of cloperastine enantiomers in rat plasma and its pharmacokinetic application
Author(s) -
Lun Jia,
Zhao Pengfei,
Jiang Zhen,
Song Yongbo,
Guo Xingjie
Publication year - 2020
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.23257
Subject(s) - chemistry , chromatography , enantiomer , pharmacokinetics , analyte , electrospray ionization , selected reaction monitoring , ammonium hydroxide , stereoselectivity , mass spectrometry , detection limit , tandem mass spectrometry , stereochemistry , pharmacology , organic chemistry , catalysis , medicine
Cloperastine is a central antitussive used to reduce the frequency and intensity of coughing on a short‐term basis. In this study, a reliable chiral LC‐MS/MS technology has been developed for the quantification of cloperastine enantiomers in the rat plasma. Carbinoxamine was selected as the internal standard. The enantioseparation of cloperastine was performed on a Chiralpak IA column with a mobile phase composed of acetonitrile‐water‐ammonium hydroxide (80:20:0.1, v / v / v ) at a flow rate of 0.6 mL/min. Cloperastine enantiomers were detected by mass spectrometry in multiple reaction monitoring mode with a positive electrospray ionization source. The method was validated over the linear concentration range of 0.05 to 10.0 ng/mL (5.0 × 10 −4 ng to 0.10 ng) for both enantiomers. The lower limit of quantification (LLOQ) for each analyte was determined as 0.05 ng/mL. The relative standard deviations (RSDs) of intraday and interday precision was less than 13.9%, and the relative error (RE) of accuracy ranged from −5.4% to 6.1%, which were within the acceptance criteria. Finally, an application to the stereoselective pharmacokinetics of cloperastine in rats was successfully realized in our assay. The developed method on a commercially available Chiralpak IA column under isocratic mobile phase is advantageous to analyze cloperastine enantiomers in plasma samples collected for enantioselective metabolism or drug interaction studies.