title: Comparison of LC-MS/MS vs chemiluminescent microparticle immunoassay in measuring the valproic acid concentration in plasma of epilepsy patients in a new perspective.
abstract: OBJECTIVE
  This study was designed to compare the performance of LC-MS/MS with chemiluminescent microparticle immunoassay (CMIA) for determination of VPA in epilepsy patients in the perspective of metabolites' hepatotoxicity.
  
  
  METHODS
  Samples were collected and then analyzed using both LC-MS/MS and CMIA. A LO2 cells (normal human hepatic cells) experiment was carried out to confirm VPA metabolites' hepatotoxicity using AST(Aspertate Aminotransferase, AST), ALT(Alanine aminotransferase, ALT) and LDH(lactate dehydrogenase, LDH) in supernate as index.
  
  
  RESULTS
  The regression equation analysis showed as LC-MS/MS=1.0094CMIA-1.8937, with the concordance correlation coefficient of 0.9700, and the CUSUM test proved no significant deviation from linearity (P>.05). CMIA compared to LC-MS/MS gave a positive bias of 1.2 μg/mL. In LO2 experiment, VPA and its metabolites groups showed an obvious increment of AST, ALT, and LDH in supernate.
  
  
  CONCLUSIONS
  The LC-MS/MS is largely consistent with the CMIA in analytical time and quantification ability for VPA, but the LC-MS/MS can simultaneously determinate VPA and its metabolites in plasma, and is also a higher cost-efficiency method in consideration of toxic metabolites monitoring. The overestimation of VPA by CMIA showed no clinical significance. The metabolites 3-OH-VPA and 5-OH-VPA damage the LO2 cells and the results presented a statistical significance (P<.05). It is vital to monitor the metabolites' concentrations for VAP's clinical safety application, and now is the occasion that laboratory and clinic consider the LC-MS/MS method as a more advantageous alternative to CMIA method in therapeutic monitoring of VPA.
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yunlei
authors.initials: Y
authors.lastname: Yun
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.|College of Chemistry and Bio-Engineering, Yichun University, Yichun, China.
authors.forename: Xinfang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.|College of Chemistry and Bio-Engineering, Yichun University, Yichun, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: You
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shouhong
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wansheng
authors.identifier: http://orcid.org/0000-0002-0025-1315
authors.initials: W
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D016014:Linear Models; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014635:Valproic Acid / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid
keywords: LC-MS/MS; LO2 experiment; VPA and its metabolites; chemiluminescent microparticle immunoassay