title: Development of a stable isotope dilution UPLC-MS/MS method for quantification of dexmedetomidine in a small amount of human plasma.
abstract: Dexmedetomidine (Dex) is a selective central α2-agonist with anesthetic properties and has been used in clinical practice for sedation in the intensive care unit (ICU) after operations. In this study, an analytical assay for the determination of Dex in a small amount of plasma was developed for the application to pediatric ICU trials. The quantification of Dex was constructed using the original stable isotope Dex-d3 for electrospray ionization-tandem mass spectrometry (ESI-MS/MS) in the selected reaction monitoring mode. A rapid ultra-performance liquid chromatography technique was adopted using ESI-MS/MS with a runtime of 3 min. Efficacious concentration levels (50 pg/mL to 5 ng/mL) could be evaluated using a very small amount of plasma (10 μL) from patients. The lower limit of the quantification was 5 pg/mL in the plasma (100 µL). For sample preparation, a solid-phase extraction was used along with the OASIS-HLB cartridge type. Recovery values ranged from 98.8 to 100.3% for the intra- [relative standard deviation (RSD), 0.9-1.3%] and inter- (RSD, 0.9-1.5%) day assays. A stable test had recovery values that ranged from 97.8 to 99.7% with an RSD of 1.0-1.9% for the process/wet extract, bench-top, freeze-thaw and long-term tests. This method was used to measure the Dex levels in plasma from pediatric ICU patients. In the clinical ICU trial, the small amount of blood (approximate plasma volume, 200 μL) remaining from blood gas analysis was reused and targeted for the clinical analysis of Dex in plasma.
authors: Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors: Koichi
authors: K
authors: Inoue
authors: Tasuku
authors: T
authors: Sakamoto
authors: Yoshihito
authors: Y
authors: Fujita
authors: Saya
authors: S
authors: Yoshizawa
authors: Maiko
authors: M
authors: Tomita
authors: Jun Zhe
authors: JZ
authors: Min
authors: Kenichiro
authors: K
authors: Todoroki
authors: Kazuya
authors: K
authors: Sobue
authors: Toshimasa
authors: T
authors: Toyo'oka
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020927:Dexmedetomidine / Q000097:blood* / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood* / Q000737:chemistry; D007223:Infant; D007553:Isotope Labeling; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine