Sensitive UHPLC-MS/SRM method for quantifying olanzapine metabolites and degradation products from sera

In recent years{,} the use of antipsychotics like olanzapine has increased leading to potentially serious adverse metabolic effects. A sensitive method to quantify olanzapine and its metabolites is therefore highly needed. A stable isotope dilution ultrahigh performance liquid chromatography-mass spectrometry/selected reaction monitoring based quantitative assay has been developed for the simultaneous estimation of olanzapine and its metabolites. This method includes the parent drug olanzapine{,} its metabolites (desmethyl olanzapine and olanzapine-N-oxide) and degradation derived piperazinium chloride{,} lactam and cyclic amine impurities. All analytes were well resolved and showed a linear relationship across a large dynamic range (0.017-1.25 ng mL-1) for all olanzapine metabolites except the lactam{,} in which the linear relationship was demonstrated at concentrations five times higher (0.085-6.25 ng mL-1). All analytes had regression coefficients higher than 0.998{,} accuracies between 92-113% and low coefficients of variation (0.94 to 9.3%). The recovery for all of the analytes from the sera matrix was 80 to 115%. This validated method is suitable for quantifying olanzapine and its metabolites from small volumes of sera samples with great sensitivity.