HPLC-MS/MS测定人血清中多种精神类药物的浓度及临床应用

Therapeutic drug monitoring and clinical application of multiple antipsychotic drugs in human serum by HPLC-MS/MS

目的建立一种快速测定人血清中多种精神类药物(利培酮、9-羟基利培酮、阿立哌唑、脱氢阿立哌唑)浓度的高效液相色谱串联质谱法(HPLC-MS/MS)。方法以利培酮-d4和阿立哌唑-d8为内标,以Waters Cortecs C_(18)(2.1×50 mm,2.7μm)为色谱柱,柱温45℃,流速0.5 ml/min,流动相为0.1%甲酸水溶液(A)~0.1%甲酸甲醇(B),梯度洗脱,快速进行治疗药物浓度监测。结果在线性范围内,多种精神类药物的线性良好(r>0.99),低、中、高值质控的日内和日间精密度的CV均小于7.21%,基质效应在91.67%~105.4%,CV小于6.15%。结论本方法操作简单快速,灵敏度高、准确度好,可在4 min中完成一次标本检测,通量高,可满足临床对多种精神类药物检测的需求。

Objective To establish a rapid method for the determination of multiple antipsychotic drugs(risperidone,9-hydroxyrisperidone,aripiprazole and dehydroaripiprazole)in human serum by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).Methods Risperidone-d4 and aripiprazole-d8 were employed as internal standards.Chromatographic separation was carried on a Waters Cortecs C_(18)(2.1×50 mm,2.7μm)column held at 45℃.The flow was set at 0.5 ml/min.The optimal mobile phase was composed of 0.1% formic acid aqueous(A)and 0.1% formic acid methanol.Therapeutic drug monitoring was rapidly conducted by the developed HPLC-MS/MS method.Results The linearity of antipsychotic drugs were good in the linear range(r>0.99).The CV of intra-day and inter-day precisions of low,middle and high quality controls were less than 7.21%.And the matrix effects of quality controls were 91.67%~105.4% with CV<6.15%.Conclusion The established method is simple manipulation with high sensitivity and accuracy.The running time is only 4 min,which could satisfy the requirement of clinical throughput for the determination of multiple antipsychotic drugs.