Comparison of LC LC ‐ MS MS / MS MS vs chemiluminescent microparticle immunoassay in measuring the valproic acid concentration in plasma of epilepsy patients in a new perspective

摘要

Objectives 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. Method Samples were collected and then analyzed using both LC ‐ MS / MS and CMIA . A LO 2 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 =1.0094 CMIA ‐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 LO 2 experiment, VPA and its metabolites groups showed an obvious increment of AST , ALT , and LDH in supernate. Conclusion 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 LO 2 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 .