Development and Validation of a Rapid LC/MS-MS Method for Measuring Plasma Quetiapine and Norquetiapine in Psychiatric Patients
Sootthikarn Mungkhunthod, MSc1, Santirhat Prommas, BSc4, Apichaya Puangpetch, PhD4, Pongsatorn Paholpak, MD2, Nontaya Nakkam, PhD1, Chonlaphat Sukasem, PhD4,5, Wichittra Tassaneeyakul, PhD1, Suda Vannaprasaht, MD1,3
Affiliation : 1Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 2Department of Psychiatry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 3Clinical Pharmacology and Toxicology Unit, Department of Medicine, Khon Kane University, Khon Kaen, Thailand, 4Division of Pharmacogenomics and Personalized Medicine, Departments of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 5Pharmacogenomics and Precision Medicine, Bumrungrad Genomic Medicine Institute (BGMI), Bumrungrad International Hospital, Bangkok, Thailand
Background: Quetiapine (QTP) is an atypical antipsychotic drug that is widely used to treat psychiatric patients. N-desalkylquetiapine (NQTP) is the major and active metabolite.
Objective: The present study aimed to develop and validate a method for measuring QTP and NQTP concentrations in human plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Materials and Methods: Plasma samples were processed using liquid-liquid extraction, and the analytes were separated on a C18 column. The analysis was conducted using a triple quadrupole tandem mass spectrometer with a mobile gradient phase consisting of 0.1% formic acid in 10 mM ammonium formate and 100% acetonitrile. The total run time was 6 min.
Results: The calibration curves for QTP and NQTP were in a linear range of 2.0 to 600.0 ng/ml. The within-run and between-run precision for QTP was 10.29% and 11.16%, whereas those for NQTP were 8.21% and 12.87%, respectively. The within-run and between-run accuracy for QTP was <111.74%, <100.34%, <110.53%, and <104.11% for NQTP, respectively. The lower limit of detection for QTP and NQTP was 2.0 ng/ml.
Conclusion: An LC-MS/MS method for measuring QTP and NQTP levels in human plasma was validated and successfully applied to measure these analytes in psychiatric patients.
Keywords : Quetiapine; Norquetiapine; Antipsychotics; LC-MS/MS; Plasma concentrations; Liquid-liquid extraction
