HPLC analysis of the novel antipsychotic drug quetiapine in human plasma R. Mandrioli a , S. Fanali b , A. Ferranti a , M.A. Raggi a, * a Dipartimento di Scienze Farmaceutiche, Universita ` di Bologna, Via Belmeloro 6, 40126 Bologna, Italy b Istituto di Metodologie Chimiche del CNR, Area della Ricerca di Roma, P.O. Box 10, 00016 Monterotondo Scalo, Roma, Italy Received 16 May 2002; received in revised form 18 June 2002; accepted 19 June 2002 Abstract A precise and feasible high-performance liquid chromatographic (HPLC) method for the analysis of the novel antipsychotic drug quetiapine in plasma has been developed. The analysis was carried out on a C8 (150 /4.6 mm i.d., 5 mm) reversed-phase column, using a mixture of acetonitrile, methanol and pH 1.9 phosphate buffer as the mobile phase; triprolidine was used as the internal standard. Careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE). A good linearity was found in the 4 /400 ng ml 1 quetiapine plasma concentration range. The application to some plasma samples of patients treated with Seroquel † tablets gave satisfactory results. The accuracy was good (quetiapine mean recovery /92%), as well as the precision (mean RSD / 3.3%). The method seems to be suitable for the clinical monitoring of patients treated with quetiapine. # 2002 Elsevier Science B.V. All rights reserved. Keywords: HPLC analysis; Antipsychotic drug; Quetiapine; Solid-phase extraction 1. Introduction The treatment of schizophrenia has made great strides with the introduction of ‘atypical’ antipsy- chotic drugs, as opposed to ‘classical’ antipsycho- tics such as chlorpromazine and haloperidol [1]; in fact, atypical antipsychotics have higher efficacy and tolerability, and have notably improved the quality of life of many patients. One of the most recently introduced atypical antipsychotics is que- tiapine (2-(2-[4-(dibenzo[b ,f ]thiazepin-11yl)pipera- zin-1-yl]ethoxy)ethanol, Fig. 1a), a drug belonging to the group of the dibenzothiazepines and struc- turally similar to clozapine, the first atypical antipsychotic (Fig. 1b). Quetiapine is mainly metabolised in the liver [2], and hepatic metabolism accounts for the forma- tion of at least 11 metabolites [3]. Quetiapine has favourable effects on both the positive (e.g. hallucinations and delusions) and the negative (e.g. poverty of speech, flat affectivity and apathy) symptoms of schizophrenia [4] with clin- ical efficacy comparable to those of chlorproma- * Corresponding author. Tel.:  /39-051-2099700; fax:  /39- 051-2099734 (Dept.) E-mail address: raggima@alma.unibo.it (M.A. Raggi). Journal of Pharmaceutical and Biomedical Analysis 30 (2002) 969  /977 www.elsevier.com/locate/jpba 0731-7085/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved. PII:S0731-7085(02)00395-3