Natchaya Vanwong1,2, Santirat Prommas1,2, Apichaya Puangpetch1,2, Yaowaluck Hongkaew1,2, Nopadol Nuntamool1,2,3, Chalitpol Na Nakorn1,2,4, Nattawat Ngamsamut5, Penkhae Limsila5, Chonlaphat Sukasem6,7. 1. Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 2. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. 3. Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand. 4. Translational Medicine, Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 5. Ministry of Public Health, Department of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Bangkok, Thailand. 6. Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. chonlaphat.suk@mahidol.ac.th. 7. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. chonlaphat.suk@mahidol.ac.th.
Abstract
BACKGROUND: Risperidone (RIS) is a widely used atypical antipsychotic drug. We developed and validated a sensitive and accurate LC-MS/MS method, which requires a small-volume of plasma and small-volume injection for measurement of RIS levels in ASD pediatric patients. We also investigated the relationship between RIS levels and RIS dosages, including prolactin levels. METHOD: Blood samples were processed by protein precipitation extraction. Only 1 μl of sample was injected. Plasma samples were separated on a C18 column (4.6 cm × 50 mm; 1.8 μm particle size). Detection was by MS-MS with an analytical run time of 6 min. RESULTS: The inter-day accuracy of RIS was 101.33-107.68% and 95.24-103.67% for 9-OH-RIS. The inter-day precision of RIS was ≤7.27% CV and ≤7.41% CV for 9-OH-RIS. The extraction recovery of RIS and 9-OH-RIS were 95.01 ± 7.31-112.62 ± 7.50% and 90.27 ± 11.15-114.00 ± 10.35%, respectively. This method was applied in the therapeutic drug monitoring of ASD pediatric patients. Higher RIS dosage has a tendency to produce higher RIS plasma levels. The high RIS plasma levels have a tendency to produce hyperprolactinemia. CONCLUSION: The determination of RIS in individual patients might be clinically useful for monitoring and prediction of treatment response.
BACKGROUND:Risperidone (RIS) is a widely used atypical antipsychotic drug. We developed and validated a sensitive and accurate LC-MS/MS method, which requires a small-volume of plasma and small-volume injection for measurement of RIS levels in ASD pediatric patients. We also investigated the relationship between RIS levels and RIS dosages, including prolactin levels. METHOD: Blood samples were processed by protein precipitation extraction. Only 1 μl of sample was injected. Plasma samples were separated on a C18 column (4.6 cm × 50 mm; 1.8 μm particle size). Detection was by MS-MS with an analytical run time of 6 min. RESULTS: The inter-day accuracy of RIS was 101.33-107.68% and 95.24-103.67% for 9-OH-RIS. The inter-day precision of RIS was ≤7.27% CV and ≤7.41% CV for 9-OH-RIS. The extraction recovery of RIS and 9-OH-RIS were 95.01 ± 7.31-112.62 ± 7.50% and 90.27 ± 11.15-114.00 ± 10.35%, respectively. This method was applied in the therapeutic drug monitoring of ASD pediatric patients. Higher RIS dosage has a tendency to produce higher RIS plasma levels. The high RIS plasma levels have a tendency to produce hyperprolactinemia. CONCLUSION: The determination of RIS in individual patients might be clinically useful for monitoring and prediction of treatment response.
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