Abstract
A rapid, robust and selective high pressure liquid chromatography–positive electrospray ionization tandem mass spectrometry method has been developed and validated for the quantification of quetiapine (QUE) in human plasma with K2EDTA using oxcarbazepine (IS) as an internal standard. Analyte and internal standard were extracted from human plasma by solid-phase extraction using acetonitrile. The eluted samples were chromatographed on a C18 column by using a 10:75:15v/v mixture of ammonium formate buffer (5 mM, pH 4.50) and acetonitrile and methanol as an isocratic mobile phase at a flow rate of 0.4 mL/min and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective [M+H]+ions,m/z384.3/253.2 for Quetiapine andm/z253.1/208.1 for the internal standard. The assay exhibited a linear dynamic range of 5.01 - 2501.04 ng/mL for quetiapine in human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze 300 patient plasma samples per day. The validated method has been successfully used for the estimation of quetiapine in real time schizophrenia patient’s plasma samples for pharmacokinetic study.
Highlights
IntroductionQuetiapine (Figure 1) is an atypical antipsychotic and is a dibenzothiazepine derivative with greater in vitro binding affinity for serotonin 5-HT2A receptors than for dopamine D2 receptors[1]
Quetiapine (Figure 1) is an atypical antipsychotic and is a dibenzothiazepine derivative with greater in vitro binding affinity for serotonin 5-HT2A receptors than for dopamine D2 receptors[1].This property is widely considered to predict atypicality, which is defined clinically as minimal or absent extrapyramidal symptoms (EPS)[2] at clinically relevant doses
Quetiapine is an antagonist at a broad range of neurotransmitter receptors[1, 4]
Summary
Quetiapine (Figure 1) is an atypical antipsychotic and is a dibenzothiazepine derivative with greater in vitro binding affinity for serotonin 5-HT2A receptors than for dopamine D2 receptors[1]. This property is widely considered to predict atypicality, which is defined clinically as minimal or absent extrapyramidal symptoms (EPS)[2] at clinically relevant doses. Cmax values for men and women at steady state were 277 and 295 ng/mL respectively with quetiapine 75 mg three times daily; 625 and 572 ng/mL with quetiapine 150 mg three times daily; 778 and 879 ng/mL with quetiapine 250 mg three times daily[5]. The highest dosage (250 mg three times daily) was associated with a mean elimination half-life of 5.8 hours in men and 6.6 hours in women
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