Lodise, Thomas P., et al. Antimicrobial agents and chemotherapy, 2021, 65(3), 10-1128.
This study evaluated the pharmacokinetic (PK) and PK-pharmacodynamic (PK-PD) target attainment of intravenous minocycline in critically ill patients with suspected or confirmed Gram-negative infections. Here we focus on the results of quantitative analysis experiments of total plasma and free plasma minocycline concentrations.
Quantitative Analysis
Total and unbound minocycline levels were measured via LC-MS/MS. Samples, spiked with the internal standard minocycline-d6, underwent liquid-liquid extraction using ethyl acetate. Minocycline and the internal standard were quantified in multiple reaction monitoring (MRM) mode, with transitions at *m/z* 458.3 → 441.0 (minocycline) and *m/z* 464.2 → 447.1 (minocycline-d6).
Key Findings
As shown in the figure to the right, the mean ± SD of the observed total and unbound plasma minocycline concentration-time data are presented on both linear and semi-logarithmic scales. The data show that total and unbound minocycline concentrations declined simultaneously in a biphasic manner after the end of the approximately 1-hour intravenous infusion. Plots of the bound minocycline fraction versus total minocycline concentration using time-matched data, including a focus on only minocycline with total minocycline concentrations less than 2 mg/L, also indicate that the unbound fraction appears to remain constant and is independent of total minocycline concentration.
