Quantitative ultra-high-performance liquid chromatography-tandem mass spectrometry for determination of dexmedetomidine in pediatric plasma samples: Correlation with genetic polymorphisms.

Autor: Guan Y; Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.; Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China., Li B; Department of Anaesthesiology, Guangzhou Women and Children's Medical Center and Guangzhou Medical University, Guangzhou, China., Wei W; Department of Anaesthesiology, Guangzhou Women and Children's Medical Center and Guangzhou Medical University, Guangzhou, China., Wang S; Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China., Yuen VM; Department of Anaesthesiology, Hong Kong Children's Hospital, Hong Kong, China., Liu Y; Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China., Ao Z; Department of Anaesthesiology, Guangzhou Women and Children's Medical Center and Guangzhou Medical University, Guangzhou, China., Zhou S; Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China., Tian H; Department of Anaesthesiology, Guangzhou Women and Children's Medical Center and Guangzhou Medical University, Guangzhou, China., Huang M; Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China., Song X; Department of Anaesthesiology, Guangzhou Women and Children's Medical Center and Guangzhou Medical University, Guangzhou, China., Zhong G; Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2019 Dec; Vol. 33 (12), pp. e4683. Date of Electronic Publication: 2019 Oct 10.
DOI: 10.1002/bmc.4683
Abstrakt: Dexmedetomidine is an important sedative agent administered as premedication to achieve procedural sedation in children. To describe the correlation between the genetic state and the concentration of dexmedetomidine, it is necessary to develop a specific, time-saving and economical method for detection of dexmedetomidine in plasma samples. In this work, an ultra-high-performance liquid chromatography (UHPLC)-tandem mass spectrometry method has been established and validated for detection of dexmedetomidine in plasma from pediatric population. After a simple liquid-liquid extraction with an organic solution, the analytes were separated on an ACQUITY BEH C 18 column (2.1 mm × 50 mm, 1.7 μm particle size) by gradient elution with the mobile phase of acetonitrile and 1‰ aqueous formic acid (flow rate 0.3 mL min -1 ). Mass spectrometry measurements were performed under the positive selected reaction monitoring and the mass transitions monitored were m/z 201.3 → 95.1, 204.2 → 98.0 for dexmedetomidine and deuterated medetomidine (internal standard), respectively. Validation of the method based on China Food and Drug Administration guidelines showed acceptable selectivity. The UHPLC method employed a stable isotope-labeled internal standard, showed good specificity and was successfully used to detect dexmedetomidine in plasma samples from 260 pediatric patients. A subsequent application of this method to a pharmacogenetic study was also described. Importantly, this is the first study to report the correlation between CYP2A6 rs835309 activity and concentration of dexmedetomidine.
(© 2019 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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