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A sensitive LC‐MS/MS method for simultaneous determination of R ‐bambuterol and its active metabolite R ‐terbutaline in human plasma and urine with application to a clinical pharmacokinetic study
Author(s) -
Zhou Ting,
Zhao Ting,
Cheng Qing,
Liu Shan,
Xu Ling,
Tan Wen
Publication year - 2014
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3107
Subject(s) - chemistry , chromatography , metabolite , terbutaline , electrospray ionization , analyte , ethyl acetate , protein precipitation , selected reaction monitoring , active metabolite , mass spectrometry , urine , ammonium acetate , tandem mass spectrometry , high performance liquid chromatography , medicine , biochemistry , asthma
A sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for simultaneous determination of R ‐bambuterol and its active metabolite R ‐terbutaline in human plasma and urine was established. The inhibition for the biotransformation of R ‐bambuterol in plasma was fully investigated. Plasma samples were prepared on ice and neostigmine metilsulfate added as a cholinesterase inhibitor immediately after sample collection. All samples were extracted with ethyl acetate and separated on a C 18 column under gradient elution with a mobile phase consisting of methanol and water containing 5 m m ammonium acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma. In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R ‐bambuterol and R ‐terbutaline, respectively. The intra‐ and inter‐day precisions were <12.7 and <8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min per sample made this method suitable for high‐throughput determination. The validated method has been successfully applied to the human pharmacokinetic study of R ‐bambuterol involving 10 healthy volunteers. Copyright © 2013 John Wiley & Sons, Ltd.