Analysis and pharmacokinetics of quetiapine and two metabolites in human plasma using reversed-phase HPLC with ultraviolet and electrochemical detection
Pc. Davis et al., Analysis and pharmacokinetics of quetiapine and two metabolites in human plasma using reversed-phase HPLC with ultraviolet and electrochemical detection, J PHARM B, 20(1-2), 1999, pp. 271-282
A sensitive and specific HPLC assay for the measurement of the antipsychoti
c compound quetiapine in human plasma has been developed and validated. The
assay employs a three-step liquid-liquid extraction of quetiapine and its
7-hydroxylated and 7-hydroxylated, N-dealkylated metabolites from human pla
sma, and utilizes ultraviolet (UV) detection of quetiapine and electrochemi
cal detection of the metabolites. The method provides a linear response fro
m a quantitation limit of 2.50 to 500 ng ml(-1) for each analyte using 0.4
mi plasma. The assay is applicable from 500 to 5000 ng ml(-1) by sample dil
ution with de-ionized water. The inter-assay precision of quetiapine in pla
sma calibration standards across 4 validation days averaged 11.9% relative
standard deviation (RSD) over the range 2.50 to 500 ng ml(-1), with intra-a
ssay precision averaging 16.0% RSD and mean accuracy of 98.6% of theory. Si
milarly, the inter-assay precision of the 7-hydroxylated metabolite in plas
ma calibration standards across 4 validation days averaged 13.7% RSD over t
he range 2.50 to 500 ng ml(-1), with intra-assay precision averaging 17.6%
RSD and mean accuracy of 109% of theory. The 7-hydroxylated, N-dealkylated
metabolite demonstrated inter-assay precision of 16.2% RSD, intra-assay pre
cision of 19.9% RSD, and mean accuracy of 104% of theory over the range 2.5
0 to 500 ng ml(-1). The present assay method was used to support a study co
mparing the pharmacokinetic profile of quetiapine with the time course of d
opamine D-2 and serotinin 5-MT2 receptor occupancy in the brain using posit
ron emission tomography (PET). We describe in this paper the bioanalytical
method and the plasma concentrations of quetiapine and its metabolites resu
lting from this study. (C) 1999 Elsevier Science B.V. All rights reserved.