Determination of Tigecycline in Plasma and Bronchoalveolar Lavage Fluid by UPLC–MS/MS and Its Application to a Pharmacokinetic Study in Critically Ill Patients

ABSTRACT Tigecycline has been widely used for treating infections caused by multidrug resistant bacteria, but the dosage and intrapulmonary distribution were still controversial. In this study, a UPLC–MS/MS method was established and fully validated to quantify tigecycline in human plasma and BALF. A simple and rapid protein precipitation was used to extract the analytes from plasma and BALF samples. Then, tigecycline and IS were separated on a SHIMADZU AQ‐C18 column and detected using electrospray ionization positive ion mode using the transitions of m / z 586.3 → 513.2 m / z for TGC and 458.0 → 441.0 m / z for minocycline (IS). The linearity of the calibration was in the range of 20–2000 ng/mL in plasma and BALF. The validated method was successfully applied to investigate pharmacokinetic characteristics of tigecycline in critically ill patients. The results suggested that after intravenous administration of 100‐mg q12h tigecycline, the AUC 0–12 was 3663.02 ± 2075.84 ng × h/mL and C ss,av was 305.25 ± 172.99 ng/mL; the average plasma concentration/ELF concentration ratio was 3.66. Significant individual differences and highly variable pharmacokinetic properties were observed, indicating that adjustment of dosing regimens according to therapeutic drug monitoring is effective and efficient to guarantee the drug efficacy and safety especially for critically ill patients.