Determination of the unstable drug otilonium bromide in human plasma by LC-ESI-MS and its application to a pharmacokinetic study.
Otilonium bromide (OB) degrades rapidly in plasma and readily undergoes hydrolysis by the plasma esterase. In this paper, an LC-ESI-MS method has been developed for the determination of OB in human plasma. The rapid degradation of OB in plasma was well prevented by immediate addition of potassium fluoride (KF, an inhibitor of plasma esterase) to the freshly collected plasma before prompt treatment with acetonitrile. The method was validated over the concentration range of 0.1-20ng/ml. The data of intra-run and inter-run precision and accuracy were within ±15%. The mean extraction recoveries for OB and the internal standard were higher than 93.0% and the matrix effects were negligible. The method has been successfully used in a pharmacokinetic study.
Zhao
Yan-Rong
YR
Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Ding
Li
L
Fan
Hong-Wei
HW
Yu
Yong
Y
Qi
Xie-Min
XM
Leng
Ye
Y
Rao
Ya-Kun
YK
D000097:Acetonitriles / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005459:Fluorides / Q000737:chemistry; D006801:Humans; D016014:Linear Models; D008297:Male; D017680:Potassium Compounds / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000097:Acetonitriles; D017680:Potassium Compounds; D000644:Quaternary Ammonium Compounds; C013934:octylonium; C033320:potassium fluoride; D005459:Fluorides; C032159:acetonitrile