Journal of Chromatography B, 856 (2007) 57–61 Detection and quantification of aripiprazole and its metabolite, dehydroaripiprazole, by gas chromatography–mass spectrometry in blood samples of psychiatric patients Hui-Ching Huang a , Chin-Hung Liu c , Tsuo-Hung Lan b,f,g , Tsung-Ming Hu b , Hsien-Jane Chiu b , Yu-Chun Wu b , Ying Lung Tseng c,d,e,∗ a Department of Pharmacy, Yu-Li Hospital, Department of Health, Hualien, Taiwan b Department of Adult Psychiatry, Yu-Li Hospital, Department of Health, Hualien, Taiwan c DopingControl Center, Tzu Chi University, Hualien, Taiwan d Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan e Center for Vascular Medicine, Tzu Chi University, Hualien, Taiwan f Institute of Genomics, National Yang-Ming University, Taipei, Taiwan g Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Miaoli, Taiwan Received 16 February 2007; accepted 16 May 2007 Available online 2 June 2007 Abstract 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, dehydroarip- iprazole, 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 dehy- droaripiprazole 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 (r 2 = 0.999) and 8 to 250 ng/ml (r 2 =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 g/l for aripiprazole and 30.1 g/l for dehydroaripiprazole. © 2007 Elsevier B.V. All rights reserved. Keywords: Aripiprazole; Dehydroaripiprazole; Detection; GC–MS; Quantification 1. Introduction Aripiprazole (Abilify TM ; 7-[4-[4-(2,3-dichlorophenyl)-1- piperazinyl] butoxy]-3,4-dihydro-2(1H)-quinolinone; C 23 H 27 Cl 2 N 3 O 2; MW 448.38) is an atypical antipsychotic agent. This drug has been approved recently by the US Food and Drug Administration (FDA) as the sixth second-generation antipsy- chotic for the treatment of schizophrenia and schizoaffective ∗ Corresponding author at: Doping Control Center and Institute of Pharma- cology and Toxicology, Tzu Chi University, 701, Section 3, Chung Yan Road, Hualien, Taiwan. Tel.: +886 3 8564640; fax: +886 3 8578167. E-mail address: ying@mail.tcu.edu.tw (Y.L. Tseng). disorders [1,2]. Dehydroaripiprazole is the main metabolite with antipsychotic activity equivalent to that of aripiprazole [3,4]. Aripiprazole is a quinolinone derivative and the chemical structures of aripiprazole and dehydroaripiprazole are shown in Fig. 1. Aripiprazole differs from other atypical antipsychotics and is considered to act as a partial dopamine D2 receptor agonist, partial serotonin1A (5-HT1A) receptor agonist and 5-HT2A receptor antagonist [1–3,5]. Because its pharmacological mech- anism is different from other second-generation antipsychotic, aripiprazole has been referred to as a third-generation antipsy- chotic and a dopamine–serotonin system stabilizer [3]. One in vitro study has shown that aripiprazole is metabolized in the liver by P450, i.e., CYP 3A4 and CYP 2D6, isoenzymes 1570-0232/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jchromb.2007.05.026