RESUMO
Objective A highly feasible and reliable ultra-high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was presented for therapeutic drug monitoring of five anti-schizophrenic drugs (aripiprazole, amisulpride, olanzapine, paliperidone and ziprasidone) simultaneously and the reference range of plasma concentration was investigated.Methods establishment and evaluation.The selectivity,accuracy,precision,stability and linear range of established UPLC-MS/MS method were evaluated according to FDA and CLSI.After a ten-month clinical application, a retrospective analysis of 253 positive samples was carried out to investigate conformance of the AGNP therapeutic reference range for Chinese patients.Results The five anti-schizophrenic drugs could be simultaneously measured by the established UPLC-MS/MS within 6 minutes.The LOQs were 0.1 to 9.0 ng/ml.The correlation coefficients were all higher than 0.997 7.The intra-day and inter-day precisions were less than 11.1%,and the recoveries ranged from 86.2% to 104.8%.The clinical results suggested the good consistency in reference range with AGNP for olanzapine, aripiprazole, paliperidone and ziprasidone.While for amisulpride, the plasma concentration level(445.2 ±231.5)ng/ml was significantly higher than the AGNP-recommended range(100 -320)ng/ml.Conclusion The established UPLC-MS/MS method was very suitable for monitoring anti-schizophrenic drugs.