Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of tigecycline in rat brain tissues

摘要

Tigecycline (TIG), a derivative of minocycline, is the first in the novel class of glycylcyclines and is currently indicated for the treatment of complicated skin structure and intra-abdominal infections. A selective, accurate and reversed-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of TIG in rat brain tissues. Sample preparation was based on protein precipitation and solid phase extraction using Supel-Select HLB (30mg/1mL) cartridges. The samples were separated on a YMC Triart C-18 column (150mm x 3.0mm. 3.0 mu m) using gradient elution. Positive electrospray ionization (ESI+) was used for the detection mechanism with the multiple reaction monitoring (MRM) mode. The method was validated over the concentration range of 150-1200ng/mL for rat brain tissue. The precision and accuracy for all brain analyses were within the acceptable limit. The mean extraction recovery in rat brain was 83.6%. This validated method was successfully applied to a pharmacokinetic study in female Sprague Dawley rats, which were given a dose of 25mg/kg TIG intraperitoneally at various time-points. Copyright (C) 2015 John Wiley & Sons, Ltd.