A high-performance liquid chromatography with electrochemical detection for the determination of olanzapine in human plasma.

Olanzapine, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, is an atypical antipsychotic drug with a high affinity for serotonin (5HT2A/2C), dopamine (D1-4), muscarinic (M1-5), histamine H1, and α1-adrenergic receptors (1). Olanzapine is indicated for the treatment of patients with schizophrenia and psychosis of a schizoaffective nature. Olanzapine is well absorbed following oral administration and reaches peak concentrations in approximately 6 h. The pharmacokinetics of olanzapine is linear and dose-proportional within the approved dosage range. Its mean half-life in healthy subject was 33 h. Olanzapine is metabolized by the cytochromes P450 (CYP), and in particular by the isozymes CYP1A2 and CYP2D6. One of the main metabolites is N-desmethylolanzapine (2). This paper describes a relatively simple and reproducible method for the determination of olanzapine in human plasma, using liquid ñ liquid extraction and electrochemical detection.