Abstract A selective, sensitive, precise and accurate liquid chromatography-tandem mass spectrometry method was developed and validated for the concurrent determination of antidiabetic drugs, empagliflozin and linagliptin in human plasma. Sample preparation was tested on several reversed-phase solid-phase extraction (SPE) sorbents with different chemistries like hydrophilic-lipophilic balance (Oasis HLB), mixed-mode cation exchange (Oasis MCX) and weak-cation exchange (Oasis WCX). SPE conditions like sample pH, washing and elution solvents were suitably optimized. Best results were obtained using Oasis MCX cartridges in terms of extraction recovery (78–88%) and matrix effects (~3.0%) for both the analytes. Chromatographic conditions for the separation of analytes and their labeled internal standards (ISs) were established on XSelect HSS Cyano (50 × 2.1 mm, 3.5 μm) column using 2 mM ammonium acetate buffer and acetonitrile as the mobile phase. Detection of analytes was achieved using electrospray ionization in the positive mode. For quantitative analysis, multiple reaction monitoring transitions were m/z 451.3 → 71.1 for empagliflozin and m/z 473.2 → 420.2 for linagliptin. Standard curve concentrations were validated in the range of 1.50–1500 ng/mL for empagliflozin and 0.015–15.0 ng/mL for linagliptin. The intra-batch and inter-batch precision (% CV) was

中文翻译：

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混合模式固相萃取结合 LC-MS/MS 测定人血浆中的恩格列净和利格列汀

摘要 开发并验证了一种选择性、灵敏、精确和准确的液相色谱-串联质谱法，用于同时测定人血浆中的抗糖尿病药物恩格列净和利格列汀。在具有不同化学性质的几种反相固相萃取 (SPE) 吸附剂上测试样品制备，例如亲水亲油平衡 (Oasis HLB)、混合模式阳离子交换 (Oasis MCX) 和弱阳离子交换 (Oasis WCX)。对样品 pH、洗涤和洗脱溶剂等 SPE 条件进行了适当优化。在两种分析物的萃取回收率 (78–88%) 和基质效应 (~3.0%) 方面，使用 Oasis MCX 小柱获得了最佳结果。使用 2 mM 醋酸铵缓冲液和乙腈作为流动相，在 XSelect HSS Cyano（50 × 2.1 mm，3.5 μm）色谱柱上建立了用于分离分析物及其标记内标 (IS) 的色谱条件。在正模式下使用电喷雾电离实现了分析物的检测。对于定量分析，empagliflozin 的多反应监测转换为 m/z 451.3 → 71.1，利格列汀的 m/z 473.2 → 420.2。恩格列净的标准曲线浓度范围为 1.50–1500 ng/mL，利格列汀的范围为 0.015–15.0 ng/mL。批内和批间精密度 (% CV) 为 对于定量分析，empagliflozin 的多反应监测转变为 m/z 451.3 → 71.1，利格列汀的 m/z 473.2 → 420.2。恩格列净的标准曲线浓度范围为 1.50–1500 ng/mL，利格列汀的范围为 0.015–15.0 ng/mL。批内和批间精密度 (% CV) 为 对于定量分析，empagliflozin 的多反应监测转换为 m/z 451.3 → 71.1，利格列汀的 m/z 473.2 → 420.2。恩格列净的标准曲线浓度在 1.50–1500 ng/mL 和利格列汀的 0.015–15.0 ng/mL 范围内进行了验证。批内和批间精密度 (% CV) 为