Cligosiban is a highly-affinity nonpeptide oxytocin receptor antagonist. In this study, a simple an sensitive LC–MS/MS method was developed and validated for the determination of cligosiban in rat plasma. The plasma samples were pretreated with acetonitrile as precipitant and then separated on an ACQUITY BEH C₁₈ column (2.1 × 50 mm, 1.7 μm) with 0.1% formic acid in water and acetonitrile as mobile phase. The analytes were monitored using selected reaction monitoring (SRM) mode with transitions at m/z 420.1→248.1 for cligosiban and m/z 304.1→161.1 for IS. The developed method showed good linearity over the concentration range of 1–1000 ng/mL with coefficient of correlation > 0.996. The lower limit of quantification (LLOQ) is 1 ng/mL. The method was validated for selectivity, precision, accuracy, recovery, and stability in accordance with FDA’s guidance. The validated assay has been successfully applied to the pharmacokinetic study of cligosiban in rat plasma after intravenous and oral administration. According to the current results, the oral bioavailability of cligosiban was 63.82%. Furthermore, the metabolites present in rat liver microsomes (RLM), human liver microsomes (HLM) and rat plasma were analyzed by UHPLC-LTQ-Orbitrap-MS method, and four metabolites structurally identified based on their accurate masses, and fragment ions. The proposed metabolic pathways of cligosiban were demethylation and glucuronidation. This study is the first report on the pharmacokinetic and metabolic information of cligosiban, which would provide insights into the effectiveness and toxicity of cligosiban.

Cligosiban是一种高度亲和力的非肽催产素受体拮抗剂。在这项研究中，开发了一种简单的灵敏的LC-MS / MS方法，并已用于测定大鼠血浆中的cligosiban的有效性。血浆样品用乙腈作沉淀剂预处理，然后在ACQUITY BEH C ₁₈色谱柱（2.1×50 mm，1.7μm）上分离，其中0.1％的甲酸在水中，乙腈作为流动相。使用选定的反应监测（SRM）模式对分析物进行监测，其中cligosiban和m / z的跃迁为m / z 420.1→248.1IS的304.1→161.1。所开发的方法在1–1000 ng / mL的浓度范围内表现出良好的线性，相关系数> 0.996。定量下限（LLOQ）为1 ng / mL。该方法已根据FDA的指导进行了选择性，精密度，准确度，回收率和稳定性的验证。经过验证的测定方法已成功地应用于大鼠静脉内和口服给药后的cligosiban的药代动力学研究。根据目前的结果，克格西班的口服生物利用度为63.82％。此外，通过UHPLC-LTQ-Orbitrap-MS方法分析了大鼠肝微粒体（RLM），人肝微粒体（HLM）和大鼠血浆中存在的代谢物，并根据其准确质量和碎片离子对四种代谢物进行了结构鉴定。拟定的clagosiban代谢途径为去甲基化和葡萄糖醛酸化。这项研究是关于cligosiban药代动力学和代谢信息的第一份报告，该报告将提供有关cligosiban的有效性和毒性的见解。