title: A high-performance liquid chromatography assay with ultraviolet detection for olanzapine in human plasma and urine.
abstract: Olanzapine is a commonly used atypical antipsychotic medication for which therapeutic drug monitoring has been proposed as clinically useful. A sensitive method was developed for the determination of olanzapine concentrations in plasma and urine by high-performance liquid chromatography with low-wavelength ultraviolet absorption detection (214 nm). A single-step liquid-liquid 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 olanzapine derivative) from the biological matrices which were adjusted to pH 10 with 1 M carbonate buffer. Detector response was linear from 1-5000 ng (r2>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, respectively. 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). Intraday 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 applicability of the assay was demonstrated by determining plasma concentrations of olanzapine in a healthy male volunteer for 48 h following a single oral dose of 5 mg olanzapine. This method is suitable for studying olanzapine disposition in single or multiple-dose pharmacokinetic studies.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Boulton
authors.forename: J S
authors.initials: JS
authors.lastname: Markowitz
authors.forename: C L
authors.initials: CL
authors.lastname: DeVane
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001569:Benzodiazepines; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine