同时测定人血清中12种抗精神病药物及其主要代谢物的方法

A method for the simultaneous determination of 12 antipsychotic drugs and their main metabolites in human serum

中文关键词:  抗精神病药物  血清药物浓度  超高效液相色谱串联质谱

英文关键词:Antipsychotic drugs  Serum drug concentration  UPLC-MS/MS

中文摘要:

      抗精神病药物及其代谢物的血药浓度监测能够指导临床用药方案的调整，有助于提高疗效，降低不良反应，然而目前还缺乏一种能够准确、高效地定量检测多种抗精神病药物及其代谢物的方法。目的 建立一种基于超高效液相色谱-串联质谱（UPLC-MS/MS）同时测定人血清中12种抗精神病药物及其主要代谢物的定量分析方法。方法 采用UPLC-MS/MS技术，使用蛋白沉淀法进行前处理，选用Agela Technologies Durashell C8色谱柱（50 mm×3.0mm，5μm），梯度洗脱进行色谱分离，流速为0.4 mL/min，总分析时长为5 min，柱温40℃。质谱检测采用多反应监测（MRM）模式，并使用同位素内标法进行定量。结果 12种抗精神病药物及其主要代谢物在低、高质量浓度下，内标归一化基质效应因子的RSD均小于15%，提取回收率为85%~115%。它们在各自的标准曲线范围内线性关系良好（r＞0.995）。在低、中、高质量浓度下，准确度为85.24%~114.71%，批内、批间精密度的RSD均≤14.15%，且稳定性较好。结论 本方法各项分析性能指标均满足验证要求，为人血清中抗精神病药物及其主要代谢物的定量检测提供了分析手段。

英文摘要:

      Therapeutic drug monitoring (TDM) of antipsychotic agents and their metabolites can guide clinical adjustment of medication regimens, thereby offering the potential to enhance therapeutic efficacy while reducing adverse effects. However, there is currently a lack of an accurate and efficient method for quantitatively detecting multiple antipsychotic drugs and their metabolites. Objective To establish a UPLC-MS/MS method for the simultaneous identification and quantitation of 12 antipsychotic drugs and their main metabolites in human serum. Methods The UPLC-MS/MS technique was employed, with protein precipitation used for pretreatment. An Agela Technologies Durashell C8 column (50 mm × 3.0 mm, 5 μm) was selected for chromatographic separation which was achieved through gradient elution at a flow rate of 0.4 mL/min, with a total analysis time of 5 min and a column temperature of 40 °C. Mass spectrometry was operated in multiple reaction monitoring (MRM) mode, and isotopic internal standard method was used for quantification. Results At both low and high concentrations, the RSD of the 12 antipsychotic drugs and their main metabolites values of internal standard normalized matrix factors were within 15%, and the extraction recovery ranged from 85% to 115%. They showed good linear relationships within their linear ranges, with linear correlation coefficients (r) > 0.995. At low, medium and high concentrations, the accuracy ranged from 85.24% to 114.71%, with intra-batch and inter-batch precisions showing RSD values below 14.15%. Stability was also satisfactory. Conclusion All analytical performance indicators of this method meet the validation requirements, providing an analytical approach for the quantitative detection of antipsychotic drugs and their main metabolites in human serum.