Simultaneous determination of quetiapine and three metabolites in human plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry.
OBJECTIVE
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 %.


CONCLUSIONS
The method is accurate, sensitive, and simple for study of pharmacokinetics and metabolic mechanism of quetiapine in patients at therapeutic dose.
Li
Kun-Yan
KY
Clinical Pharmaceutical Research Institute, Xiangya Second Hospital, Central South University, Changsha 410011, China. lkunyan@163.net
Cheng
Ze-Neng
ZN
Li
Xin
X
Bai
Xue-Lian
XL
Zhang
Bi-Kui
BK
Wang
Feng
F
Li
Huan-De
HD
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003987:Dibenzothiazepines / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D000069348:Quetiapine Fumarate; D021241:Spectrometry, Mass, Electrospray Ionization
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate