A fast and simple method for the simultaneous analysis of midazolam, 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, plasma and urine
نویسندگان
چکیده
For the quantification of sedative and anesthetic drug midazolam its main (active) metabolites 1-hydroxymidazolam, 4-hydroxymidazolam 1-hydroxymidazolam glucuronide in human serum, EDTA plasma, heparin plasma urine a single accurate method by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed. Protein precipitation as sample preparation, without need time-consuming deglucuronidation step for glucuronide, resulted simple rapid assay suitable clinical practice with total runtime only 1.1 min. The four components isotope-labeled internal standards were separated on C18 column detection was performed triple-stage quadrupole spectrometer operating positive ionization mode. validated based “Guidance Industry Bioanalytical Method Validation” (Food Drug Administration, FDA) “Guideline bioanalytical validation” European Medicines Agency (EMA). Linearity proven over ranges 5–1500 μg/L midazolam, 25–5000 using volume 100 μL. Matrix comparison indicated that is also applicable to other matrices like urine. Stability experiments showed good results stability stored 7 days under different conditions. At room temperature, 4-hydroxymidazo-lam stable but 3 serum less than 24 h All compounds found be after preparation freeze–thaw cycles. applied therapeutic monitoring (pediatric) intensive care patients.
منابع مشابه
Characterization of 1'-hydroxymidazolam glucuronidation in human liver microsomes.
Midazolam is a potent benzodiazepine derivative with sedative, hypnotic, anticonvulsant, muscle-relaxant, and anxiolytic activities. It undergoes oxidative metabolism catalyzed almost exclusively by the CYP3A subfamily to a major metabolite, 1'-hydroxymidazolam, which is equipotent to midazolam. 1'-Hydroxymidazolam is subject to glucuronidation followed by renal excretion. To date, the glucuron...
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The CYP3A subfamily represents the most abundant cytochrome p450 in the human liver and gastrointestinal tract and plays very important role in xenobiotic metabolism. CYP3A5 is expressed in a relatively small population of whites and Orientals. We recruited 42 Chinese volunteers to determine the genotypes of CYP3A5 by polymerase chain reaction-restriction fragment length polymorphism. Genotype ...
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ژورنال
عنوان ژورنال: Journal of Chromatography B
سال: 2021
ISSN: ['1570-0232', '1873-376X']
DOI: https://doi.org/10.1016/j.jchromb.2020.122476