A high-performance liquid chromatography assay with ultraviolet detection for olanzapine in human plasma and urine

Olanzapine is a commonly used atypical antipsychotic medication for which t herapeutic drug monitoring has been proposed as clinically useful. A sensit ive method was developed for the determination of olanzapine concentrations in plasma and urine by high-performance liquid chromatography with low-wav elength ultraviolet absorption detection (214 nm). A single-step liquid-liq uid extraction procedure using heptane-iso-amyl alcohol (97.5:2.5 v/v) was employed to recover olanzapine and the internal standard (a 2-ethylated ola nzapine derivative) from the biological matrices which were adjusted to pH 10 with 1 M carbonate buffer. Detector response was linear from 1-5000 ng ( r(2)>0.98). The limit of detection of the assay (signal:noise=3:1) and the lower limit of quantitation were 0.75 ng and 1 ng/ml of olanzapine, respect ively. Interday variation for olanzapine 50 ng/ml in plasma and urine was 5 .2% and 7.1% (n=5), respectively, and 9.5 and 12.3% at 1 ng/ml (n=5), Intra day variation for olanzapine 50 ng/ml in plasma and urine was 8.1% and 9.6% (n=15), respectively, and 14.2 and 17.1% at 1 ng/ml (n=15). The recoveries of olanzapine (50 ng/ml) and the internal standard were 83 +/-6 and 92 +/- 6% in plasma, respectively, and 79 +/-7 and 89 +/-7% in urine, respectively . Accuracy was 96% and 93% at 50 and 1 ng/ml, respectively. The applicabili ty of the assay was demonstrated by determining plasma concentrations of ol anzapine in a healthy male volunteer for 48 h following a single oral dose of 5 mg olanzapine. This method is suitable for studying olanzapine disposi tion in single or multiple-dose pharmacokinetic studies. (C) 2001 Elsevier Science B.V. All rights reserved.