Determination of dexmedetomidine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a pharmacokinetic study.
A rapid, sensitive and selective high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method (HPLC-ESI-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine (DMED) in human plasma. Dexmedetomidine and the internal standard (ondansetron) were extracted in a single step with diethyl-ether from 1.0 mL of alkalinized plasma. The mobile phase was a mixture of acetonitrile and 0.5% formic acid solution (30:70, v/v) at a flow rate of 0.2 mL min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer in the selected reaction monitoring (SRM) mode using the respective [M+H]+ ions m/z 201.0-->95.1 for DMED and m/z 294.1-->170.1 for the IS. The assay exhibited a linear dynamic range of 5-5000 pg mL(-1) with the correlation coefficient above 0.9995. The lower limit of quantification (LLOQ) was 5 pg mL(-1) with a relative standard deviation of less than 15%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated HPLC-MS/MS method has been successfully applied to study the pharmacokinetics of three level doses of DMED in Chinese healthy volunteers.
Li
Wenjing
W
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, PR China.
Zhang
Zunjian
Z
Wu
Lili
L
Tian
Yuan
Y
Feng
Shudan
S
Chen
Yun
Y
D000097:Acetonitriles / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020927:Dexmedetomidine / Q000097:blood* / Q000493:pharmacokinetics*; D004355:Drug Stability; D005260:Female; D005561:Formates / Q000737:chemistry; D006801:Humans; D007477:Ions; D008297:Male; D008956:Models, Chemical; D017294:Ondansetron / Q000032:analysis / Q000097:blood; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000097:Acetonitriles; D005561:Formates; D007477:Ions; C030544:formic acid; D017294:Ondansetron; D020927:Dexmedetomidine; C032159:acetonitrile