Development and Validation of HPLC-MS/MS Method for Simultaneous Quantitation of Eleven Antipsychotics in Human Plasma / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop and validate an HPLC-MS/MS method for the measurement of 11 antipsychotics in human plasma samples for TDM(therapeutic drug monitoring) or other objectives. METHODS: Protein precipitation method with acetonitrile was used to extract the drugs in plasma. Agilent Poroshell 120 EC-C18 column(2.1 mm×50 mm, 2.7 μm)was used for chromatographic separation. The mobile phase was acetonitrile with 0.1% formic acid-water with 0.1% formic acid gradiently eluted at a flow rate of 0.3 mLmin-1. The injection volume was 5 μL. The deprotonated ions of analytes were ionized by electrospray(ESI) and detected in positive ionization by multiple reaction monitoring mode(MRM). RESULTS: The total run time of the chromatographic separation and mass detection was 6 min. Excellent linear relationship with correlation coefficient of 0.99 was obtained from 2 to 200 ngmL-1 for risperidone, paliperidone and olanzapine, from 10 to 1 000 ngmL-1 for aripiprazole, quetiapine, amisulpride, clozapine, chlorpromazine and sulpride, from 0.4 to 40 ngmL-1 for haloperidol, and 0.2 to 20 ngmL-1for perphenazine, respectively. The precision and accuracy varied from 2.7% to 10.8% and from 90.7% to 102.7%, respectively. CONCLUSION: This established method is simple, rapid, and economic, fulfilling all criteria for TDM, and could be successfully applied in the routine TDM of antipsychotics in clinic.