Assay of Olanzapine in Human Plasma by a Rapid and Sensitive Gas Chromatography-Nitrogen Phosphorus Selective Detection (GC-NPD) Method

Abstract

A gas chromatography-nitrogen phosphorus selective detection (GC-NPD) method with a simple 1-step sample preparation was developed for the assay of the antipsychotic drug olanzapine in plasma. Within a time of analysis of 7 minutes, an HP-5 fused-silica capillary (25 m x 0.2 mm ID, 0.33-microm film thickness, 0.7 mL N2 as carrier gas) provided selectivity with respect to about 30 psychotropic drugs and the internal standard ethylolanzapine. Calibration was linear between 1 and 50 ng/mL and crossed the origin (LOD = 0.3 ng/mL). Intraday precision was 6.7%, 2.7%, and 1.4% at plasma concentrations of 1, 5, and 50 ng/mL, respectively. Interday precision was 4.6% at 20 ng/mL. Accuracy in commercial interlaboratory tests was 108.7% and 88.5%. The method also provided good accuracy in comparison with an HPLC method for patient samples (slope 1.003, r = 0.953) and spiked samples (slope 0.881, r = 0.998). GC-NPD with a simple sample preparation is regarded as an alternative for the assay of olanzapine plasma concentrations in therapeutic drug monitoring (TDM) and in pharmacokinetic studies. Smokers and patients taking concomitant carbamazepine had reduced plasma concentrations of olanzapine. Women and patients older than 60 years had increased plasma olanzapine concentrations.