High throughput identification and quantification of 16 antipsychotics and 8 major metabolites in serum using ultra-high performance liquid chromatography-tandem mass spectrometry.

Abstract Background Therapeutic drug monitoring of antipsychotics is important for optimizing therapy, explaining adverse effects, non-response or poor compliance. We developed a UHPLC–MS/MS method for quantification of 16 commonly used and recently marketed antipsychotics and 8 metabolites in serum. Methods After liquid–liquid extraction using methyl tert -butyl ether, analysis was performed on an Agilent Technologies 1290 Infinity LC system coupled with an Agilent Technologies 6460 Triple Quadrupole MS. Separation with a C18 column and gradient elution at 0.5 mL/min resulted in a 6-min run-time. Detection was performed in dynamic MRM, monitoring 3 ion transitions per compound. Isotope labeled internal standards were used for every compound, except for bromperidol and levosulpiride. Results Mean recovery was 86.8%. Matrix effects were − 18.4 to + 9.1%. Accuracy ranged between 91.3 and 107.0% at low, medium and high concentrations and between 76.2 and 113.9% at LLOQ. Within-run precision was Conclusions The liquid–liquid extraction and UHPLC–MS/MS technique allows robust target screening and quantification of 23 antipsychotics and metabolites.