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.

中文翻译：

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对映体选择性LC-MS / MS法测定大鼠血浆中氯哌斯丁对映体的含量及其药代动力学应用。

氯芬斯汀是一种中央镇咳药，可用于短期减少咳嗽的频率和强度。在这项研究中，已经开发出了一种可靠的手性LC-MS / MS技术，用于定量大鼠血浆中的氯吡斯汀对映体。选择羧甲基胺作为内标。在一个Chiralpak IA色谱柱上以0.6 mL / min的流速在由乙腈-水-氢氧化铵（80：20：0.1，v / v / v）组成的流动相上进行氯吡汀对映体分离。使用正电喷雾电离源，通过质谱在多重反应监测模式下检测到了氯哌汀对映体。该方法在0.05至10.0 ng / mL的线性浓度范围内（5.0×10 ^-4ng对0.10 ng）。每种分析物的定量下限（LLOQ）确定为0.05 ng / mL。日内和日间精度的相对标准偏差（RSD）小于13.9％，精度的相对误差（RE）介于-5.4％至6.1％之间，均在接受标准之内。最终，在我们的测定中成功实现了氯吡汀在大鼠体内的立体选择性药代动力学的应用。在等度流动相下在市售的Chiralpak IA色谱柱上开发的方法有利于分析血浆样品中的氯吡斯汀对映体，以用于对映选择性代谢或药物相互作用研究。