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

Abstract
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.
AuthorsRong Shao, Xingang Li, Yangmin Hu, Jinliang Chen, Honggang Lou, Haibin Dai
JournalBiomedical chromatography : BMC (Biomed Chromatogr) Vol. 32 Issue 2 (Feb 2018) ISSN: 1099-0801 [Electronic] England
PMID28677837 (Publication Type: Journal Article)
CopyrightCopyright © 2017 John Wiley & Sons, Ltd.
Chemical References
  • Anti-Bacterial Agents
  • Tigecycline
  • Minocycline
Topics
  • Anti-Bacterial Agents (blood, chemistry, pharmacokinetics, therapeutic use)
  • China
  • Chromatography, Liquid (methods)
  • Cross Infection (drug therapy)
  • Female
  • Humans
  • Linear Models
  • Male
  • Minocycline (analogs & derivatives, blood, chemistry, pharmacokinetics, therapeutic use)
  • Pneumonia, Bacterial (drug therapy)
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry (methods)
  • Tigecycline

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