Determination of Tigecycline in Human Plasma by LC-MS/MS and Its Clinical Application / 中国药房

ABSTRACT

OBJECTIVE:To establish the method for the determination of tigecycline (TGC) in human plasma. METHODS:After precipitated by acetonitrile,the plasma sample was determined by LC-MS/MS. Using d9-TGC as internal standard,Kromasil C18 column was used with mobile phase consisted of water (containing 0.05% TFA)-acetonitrile (gradient elution) at flow rate of 0.6 ml/min,column temperature of 40 ℃. The ion transitions were performed under ESI positive MRM model at m/z 586.3→513.2 and m/z 595.3→514.3 for TGC and internal standard,respectively. RESULTS:The linear range of TGC was 25-2 000 ng/ml (r=0.999 8),and lowest quantification limit was 25 ng/ml;intra-day and inter-day RSD was 3.15%-7.23%,and relative error was-4.53%-10.48%. Plasma sample kept stable after 3 times of freezing and thawing cycle,at room temperature for 24 h,in automat-ic sample injector for 24 h and freezing for 42 d (RSD<15%). Plasma concentration of TGC was 0-438.0 ng/ml in one patient with pan-drug resistant bacteria infection(0-12 h after administration). CONCLUSIONS:The developed method is accurate,sensi-tive and specific,and can be used for plasma concentration determination of TGC and pharmacokinetic study.