Development and validation of solid-phase extraction coupled with a liquid chromatography-tandem mass spectrometry method for quantitation of olanzapine in saliva

Abstract

Olanzapine is one of the most commonly used drugs for the treatment of schizophrenia and depression of various origins. Its levels are usually measured in the blood, but the collection of this diagnostic material poses many problems. Therefore, we aimed to develop a fast and sensitive method to determine olanzapine levels in saliva, an easily available diagnostic material. To reduce the consumption of toxic solvents during analyte extraction from saliva, olanzapine was isolated by solid-phase extraction using Oasis® MCX cartridges. Chromatographic analysis was performed by LC-MS/MS, with C18 resin in Atlantis® T3 column as the stationary phase and 2 mM ammonium formate and acetonitrile as the mobile phase (flow rate of 0.25 mL/min, with elution gradient). The specificity, linearity, sensitivity, precision, accuracy, and stability of the optimized method were validated. The relative standard deviation for intra-day precision for three tested olanzapine concentrations did not exceed 12.7%; the highest accuracy value was 113.9%. The recoveries from spiked saliva samples were greater than 87.3% for the two olanzapine concentrations studied. The developed method was then used to determine olanzapine levels in human saliva obtained from 15 patients treated with different doses of olanzapine.