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Highly sensitive assay for tiotropium, a quaternary ammonium, in human plasma by high‐performance liquid chromatography/tandem mass spectrometry
Author(s) -
Wang Jiang,
Jiang Yao,
Wang Yingwu,
Li Hao,
Fawcett J. Paul,
Gu Jingkai
Publication year - 2007
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.3021
Subject(s) - chemistry , chromatography , ammonium acetate , high performance liquid chromatography , formic acid , extraction (chemistry) , pharmacokinetics , liquid chromatography–mass spectrometry , tandem mass spectrometry , solid phase extraction , acetonitrile , clenbuterol , mass spectrometry , pharmacology , medicine
Tiotropium bromide, a long‐acting inhaled bronchodilator analogous to ipratropium bromide, is currently undergoing development for the treatment of chronic obstructive pulmonary disease. To evaluate its systemic absorption in humans, we have developed a rapid and sensitive method for its determination in human plasma based on high‐performance liquid chromatography with tandem mass spectrometric detection (HPLC/MS/MS). Reversed‐phase chromatography of tiotropium and the internal standard clenbuterol was carried out using acetonitrile/10 mM ammonium acetate (1% formic acid) 40:60 as mobile phase in a run time of 3.0 min. The sample preparation involved deproteination with acetonitrile, extraction into dichloromethane and back‐extraction into hydrochloric acid. The assay was linear over the concentration range 0.500–50.0 pg/mL with intra‐ and inter‐day precision (as relative standard deviation) both ≤7.34%. The method was successfully applied to a pharmacokinetic study of systemic absorption in healthy male volunteers given a single 18 µg inhaled dose. Copyright © 2007 John Wiley & Sons, Ltd.