Ultra-high performance liquid chromatography tandem mass spectrometry method for detection of anti-schizophrenic drugs and the evaluation of their therapeutic reference ranges

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.(Chin J Lab Med, 2017, 40: 787-792) Key words: Antipsychotic agents; Plasmaconcentration; Drug monitoring; Chromatography, high pressure liquid; Tandem mass spectrometry; Reference values