Liquid Chromatography-Mass Spectrometry Method for the Determination of Olanzapine in Human Plasma and Application to a Bioequivalence Study

Abstract

A rapid, sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the identification and determination of olanzapine (OLZ, CAS 132539-06-1) in human plasma. Following liquid- liquid extraction, OLZ and loratadine (IS, CAS 79794-75-5) were separated using a mobile phase consisting of acetonitrile: aqueous ammonium acetate solution (pH 4.0, 10 mM) = 56:44 (v/v) on an Agilent ZORBAX Eclipse XDB-CN (2.1mmx150mm I.D., 5μm) column and analyzed by electrospray ionization mass spectrometry in the selected ion monitoring (SIM) mode using the respective [M+H]+ ions, m/z 313.15 for OLZ and m/z 383.00 for loratadine. The chromatographic separation was achieved in less than 6.0 min. The assay exhibited a linear dynamic range of 0.5–50 ng/ml for OLZ in human plasma and had good accuracy and precision. Both intra- and inter-batch standard deviations were less than 15%. The validated LC–MS method was first applied to a bioequivalence study in 20 healthy male Chinese volunteers. Keywords: Application, Bioequivalence, Chinese volunteers, Determination, Identification, Human plasma, LC-MS, Loratadine, Olanzapine, Pharmacokinetics