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Aim: To study the multiple dose pharmacokinetics of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N-dealkyl-metabolites in Chinese suffering from schizophrenia., Methods: Twenty-one patients (11 females and 10 males) were given quetiapine twice daily to control the symptoms. After the dose reached 200 mg twice daily, blood were sampled to study the pharmacokinetics. The plasma concentrations of quetiapine and its metabolites were assayed by HPLC-MS., Results: The main pharmacokinetic parameters of quetiapine, 7-hydroxy-N-dealkyl-quetiapine, quetiapine sulfoxide, and 7-hydroxy-quetiapine were as follows: tmax were 2.0 (0.3-5.0), 4.0 (1.5-6.0), 3.0 (0.5-5.0), and 3.0 (0.5-5.0) h respectively; t1/2 were (7+/-3), (9.4+/-2.7), (7+/-3), and (8+/-5) h, respectively; Cmax(SS) were (678+/-325), (19+/-5), (451+/-216), and (58+/-22) microg/L, respectively; Cmin(SS) were (51+/-68), (3.3+/-1.6), (35+/-36), and (5+/-4) microg/L, respectively; Cav(SS) were (295+/-144), (13+/-4), (209+/-71), and (28+/-9) micro/L, respectively; AUC(0-12)(SS) were (3,538+/-1 728), (153+/-44), (2,512+/-854), and (335+/-104) microg.h.L(-1), respectively; AUC(0-infinite)(SS) were (5,534+/-4 198), (287+/-107), (3,858+/-2 012), and (529+/-262) microg.h.L(-1), respectively; Ke were (0.11+/-0.03), (0.079+/-0.019), (0.11+/-0.03), and (0.103+/-0.028) h(-1), respectively; CL/F and V/F of quetiapine were (67+/-25) L.h(-1) and (672+/-394) L, respectively. The plasma concentrations for the four compounds reached a steady state within 48 h at the dose of 200 mg initiation. These parameters were not statistically different between genders., Conclusions: Quetiapine was absorbed quickly, distributed widely, and metabolized mainly to be quetiapine sulfoxide. The elimination speeds of quetiapine and its three metabolites were similar. Gender had no effect on the pharmacokinetics of quetiapine and its metabolites. The clinical dosage regime caused no drug accumulation.

Aim: To develop a high performance liquid chromatography-electrospray mass spectrometry (HPLC-MS/ESI) method for simultaneous determination of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N-dealkyl-metabolites in human plasma., Methods: The HPLC separation of the compounds was performed on a Kromasil C18, (5 microm, 4.6 mm.150 mm) column, using water (formic acid: 1.70 mmol/L, ammonium acetate: 5.8 mmol/L)-acetonitrile (65:35) as mobile phase, with a flow-rate of 0.95 mL/min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer and detected in the selected ion recording (SIR) mode. The samples were extracted using solid-phase extraction columns., Results: The calibration curves were linear in the ranges of 10-2000 microg/L for quetiapine, 1-200 microg/L for its metabolites, respectively. The average extraction recoveries for all the four samples were above 85 %. The methodology recoveries were much higher than 95 %. The intra-day and inter-day RSD are less than 15 %., Conclusion: The method is accurate, sensitive, and simple for study of pharmacokinetics and metabolic mechanism of quetiapine in patients at therapeutic dose.