Development and validation of a sensitive assay for analysis of midazolam, free and conjugated 1-hydroxymidazolam and 4-hydroxymidazolam in pediatric plasma: Application to Pediatric Pharmacokinetic Study

摘要

Highlights?A quantitative LC-MS/MS assay for midazolam and its metabolites in pediatric plasma.?β-glucuronidase employed to measure total hydroxymidazolam metabolites.?Solid phase extraction with μ-elution plates provided a robust sample cleanup.?Pharmacokinetic profile of midazolam and its metabolites in a critically ill child.AbstractPharmacokinetic, pharmacodynamic and pharmacogenomic studies of midazolam are currently being performed in critically ill children to find suitable dose regimens. Sensitive assays using small volumes of plasma are necessary to determine the concentrations of midazolam and its respective metabolites in pediatric studies. Midazolam is metabolized to hydroxylated midazolam isomers, which are present as free as well as the corresponding glucuronide conjugates. A high-performance liquid chromatographic method with tandem mass spectrometry has been developed and validated