title: Development and Validation of Liquid Chromatography/Tandem Mass Spectrometry Analysis for Therapeutic Drug Monitoring of Risperidone and 9-Hydroxyrisperidone in Pediatric Patients with Autism Spectrum Disorders.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The determination of RIS in individual patients might be clinically useful for monitoring and prediction of treatment response.
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Natchaya
authors.initials: N
authors.lastname: Vanwong
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Santirat
authors.initials: S
authors.lastname: Prommas
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Apichaya
authors.initials: A
authors.lastname: Puangpetch
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Yaowaluck
authors.initials: Y
authors.lastname: Hongkaew
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.|Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Nopadol
authors.initials: N
authors.lastname: Nuntamool
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.|Translational Medicine, Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chalitpol Na
authors.initials: CN
authors.lastname: Nakorn
authors.affiliation: Ministry of Public Health, Department of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Bangkok, Thailand.
authors.forename: Nattawat
authors.initials: N
authors.lastname: Ngamsamut
authors.affiliation: Ministry of Public Health, Department of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Bangkok, Thailand.
authors.forename: Penkhae
authors.initials: P
authors.lastname: Limsila
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. chonlaphat.suk@mahidol.ac.th.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. chonlaphat.suk@mahidol.ac.th.
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D000067877:Autism Spectrum Disorder / Q000097:blood* / Q000188:drug therapy; D002853:Chromatography, Liquid; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D000068882:Paliperidone Palmitate / Q000097:blood* / Q000627:therapeutic use; D018967:Risperidone / Q000097:blood* / Q000627:therapeutic use; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: 9-hydroxyrisperidone; Autism spectrum disorders; LC-MS/MS; prolactin; risperidone