Detection and quantification of aripiprazole and its metabolite, dehydroaripiprazole, by gas chromatography–mass spectrometry in blood samples of psychiatric patients

Aripiprazole is a novel antipsychotic drug for the treatment of schizophrenia and schizoaffective disorders. In this study, a new method using gas chromatography–mass spectrometry (GC–MS) was developed and validated for the detection of aripiprazole and its main metabolite, dehydroaripiprazole, in plasma. Blood samples from seven psychiatric patients treated with aripiprazole (10–20 mg/day) underwent a solid-phase extraction (SPE) and N-methyl-N-trimethylsilytrifluoroacetamide (MSTFA) derivatization. The characteristic ions of mass spectra for aripiprazole and dehydroaripiprazole were m/z 306, 292, 218 and 304, 290, 218, respectively. Extraction recoveries from this method were 75.4% (n = 5) for aripiprazole and 102.3% (n = 5) for dehydroaripiprazole. The calibration curves of aripiprazole and dehydroaripiprazole were linear from 16 to 500 ng/ml (r2 = 0.999) and 8 to 250 ng/ml (r2 = 0.999), respectively. The respective limits of quantification (LOQs) for aripiprazole and dehydroaripiprazole evaluated in 0.5 ml of serum were 14.4 ng/ml and 6.9 ng/ml. Intra-assay and interassay precision and accuracy were within acceptable ranges. In this study, we also found that the mean trough concentrations in plasma at steady-state were 128.9 μg/l for aripiprazole and 30.1 μg/l for dehydroaripiprazole.