Carvedilol is a commonly used antihypertensive whose oral absorption is limited by low solubility and significant first-pass metabolism. This work aimed to apply chemometrics for the optimization of a salting-out assisted liquid–liquid extraction (SALLE) combined with LC-MS/MS to analyze carvedilol enantiomers in plasma samples. Method development and validation were driven for application in pharmacokinetic studies. Parameters that influence the efficiency of SALLE were evaluated using a fractional factorial 24–1 design with 4 factors and a central composite design was used to evaluate the optimal extraction condition. Carvedilol enantiomers and the internal standard lidocaine were separated on an Astec® Chirobiotic® V column and a mixture of methanol:ethanol (90:10, v/v) with 0.02% diethylamine and 0.18% acetic acid as mobile phase. The positive ion mode on electrospray ionization was used to monitor the transitions of m/z 407 > 100 and 235 > 86 for carvedilol enantiomers and lidocaine, respectively. Acetonitrile and ammonium acetate solution were selected for sample preparation by SALLE. Surface graphs and the desirability test were used to define the optimized SALLE conditions which resulted in 93% recovery for both carvedilol enantiomers. The method was linear in the range of 0.5 to 100 ng/mL in plasma, with a lower limit of quantification of 0.5 ng/mL. Within-run and between-run precision (as the relative standard deviation) were all < 9.74% and accuracy (as relative error) did not exceed ± 10.30%. Residual effect and matrix effect were not observed. Carvedilol enantiomers were stable in plasma under the storage, preparation, and analysis conditions. The validated method was successfully applied to analyze carvedilol in plasma samples from patients previously submitted to a Roux-en-Y gastric bypass surgery treated with a single oral dose of 25 mg racemic-carvedilol. Higher plasma concentrations were observed for (R)-(+)-carvedilol when compared to (S)-(-)-carvedilol in two patients post-bariatric surgery.

卡维地洛是一种常用的抗高血压药物，其口服吸收受限于溶解度低和显着的首过代谢。这项工作旨在应用化学计量学优化盐析辅助液液萃取 (SALLE) 结合 LC-MS/MS 分析血浆样品中的卡维地洛对映异构体。方法开发和验证被推动用于药代动力学研究。使用具有 4 个因素的部分因子 24-1 设计评估影响 SALLE 效率的参数，并使用中心复合设计评估最佳提取条件。卡维地洛对映异构体和内标利多卡因在 Astec® Chirobiotic® V 色谱柱上分离，甲醇:乙醇 (90:10, v/v) 与 0.02% 二乙胺和 0.18% 乙酸的混合物作为流动相。米/ z卡维地洛对映体和利多卡因分别为 407 > 100 和 235 > 86。SALLE 选择乙腈和乙酸铵溶液进行样品制备。表面图和合意性测试用于定义优化的 SALLE 条件，这导致两种卡维地洛对映体的回收率为 93%。该方法在血浆中 0.5 至 100 ng/mL 范围内呈线性，定量下限为 0.5 ng/mL。批内和批间精度（作为相对标准偏差）均 < 9.74%，准确度（作为相对误差）不超过 ± 10.30%。没有观察到残留效应和基质效应。在储存、制备和分析条件下，卡维地洛对映异构体在血浆中是稳定的。经验证的方法成功地应用于分析先前接受过 Roux-en-Y 胃旁路手术的患者血浆样本中的卡维地洛，这些患者接受了单次口服剂量的 25 mg 外消旋卡维地洛治疗。观察到较高的血浆浓度（R )-(+)-卡维地洛与 ( S )-(-)-卡维地洛相比，在两名患者接受减肥手术后。