Quantitative analysis and pharmacokinetics study of tigecycline in human serum using a validated sensitive liquid chromatography with tandem mass spectrometry method

J Sep Sci. 2014 Jun;37(12):1396-403. doi: 10.1002/jssc.201400152. Epub 2014 Apr 25.

Abstract

Tigecycline, a novel intravenously administered glycylcycline antibiotic, currently plays a key role in the management of complicated multiorganism infections. However, current liquid chromatography with tandem mass spectrometry methods briefly describe parameters and the only reported internal standard was sometimes difficult to obtain. In our study, an updated liquid chromatography with tandem mass spectrometry method for the quantitative analysis of tigecycline in human serum was developed. Sample preparation involved precipitation with 20% trichloroacetic acid. Chromatographic separation of tigecycline and tetracycline (internal standard) was achieved on a Hypersil GOLD C18 column using gradient elution. The selected reaction monitoring transitions were performed at m/z 586.1→513.2 for tigecycline and m/z 445.1→410.2 for tetracycline. The assay was linear over the concentration range of 5-2000 ng/mL. The intra- and interday precisions at three concentration levels (10, 100, and 1600 ng/mL) were <15% and their accuracies were within the range of 95.1-106.1%. The mean recovery ranged from 94.3 to 105.6% and the matrix effect from 92.1 to 97.6%. Tigecycline was stable under all tested conditions. This validated method was successfully applied to a pharmacokinetic study in critically ill patients. The data demonstrated that our method allows quantification of tigecycline in serum in a quick and reliable manner for widespread application.

Keywords: Intensive care medicine; Pharmacokinetics; Tetracycline; Tigecycline; liquid chromatography with tandem mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Minocycline / analogs & derivatives*
  • Minocycline / blood
  • Minocycline / pharmacokinetics
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*
  • Tigecycline

Substances

  • Tigecycline
  • Minocycline