Determination of tigecycline in human plasma by LC–MS/MS and its application to population pharmacokinetics study in Chinese patients with hospital‐acquired pneumonia

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EarlyView Article

  • Published: Aug 21, 2017
  • Author: Rong Shao, Xingang Li, Yangmin Hu, Jinliang Chen, Honggang Lou, Haibin Dai
  • Journal: Biomedical Chromatography


A selective, sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the determination of tigecycline (TGC) in human plasma, using tigecycline‐d9 as an internal standard (IS). Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The analyte and IS were separated on a reversed‐phase Waters Acquity UPLC® BEH‐C18 column (2.1 × 50 mm i.d., 1.7 μm) with a flow rate of 0.25 mL/min. The mobile phase consisted of water, containing 0.2% formic acid (v/v) with 10 mm ammonium formate (A) and acetonitrile (B). The mass spectrometer was operated in selected reaction monitoring mode through electrospray ionization ion mode using the transitions of m/z 586.2 → 513.1 and m/z 595.1 → 514.0 for TGC and IS, respectively. The linearity of the method was in the range of 10–5000 ng/mL. Intra‐ and inter‐batch precision (CV) for TGC was <9.27%, and the accuracy ranged from 90.06 to 107.13%. This method was successfully applied to the analysis of samples from hospital‐acquired pneumonia patients treated with TGC, and a validated population pharmacokinetic model was established. This developed method could be useful to predict pharmacokinetics parameters and valuable for further pharmacokinetics/pharmacodynamics studies.

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