Development and validation of an UPLC-MS/MS assay for the simultaneous quantification of seven commonly used antibiotics in human plasma and its application in therapeutic drug monitoring.

Objective: To develop and validate an UPLC-MS/MS assay for simultaneous determination of the total concentration of ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, tazobactam, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim, and the protein-unbound concentration of flucloxacillin, in human plasma to be used for research and clinical practice.

Methods: Sample pretreatment included protein precipitation with methanol. For the measurement of protein-unbound flucloxacillin, ultrafiltration was performed at physiological temperature.

Highly sensitive quantification of pemetrexed in human plasma using UPLC-MS/MS to support microdosing studies.

Pemetrexed is an antifolate drug approved for the treatment of non-small-cell lung cancer and mesothelioma. Assessing pemetrexed pharmacokinetics after administration of a microdose (100 μg) may facilitate drug-drug interaction and dose individualization studies with cytotoxic drugs, without causing harm to patients. Therefore, a highly sensitive bioanalytical assay is required.

Determination of protein-unbound, active rifampicin in serum by ultrafiltration and Ultra Performance Liquid Chromatography with UV detection. A method suitable for standard and high doses of rifampicin.

Rifampicin is the most important antibiotic in use for the treatment of tuberculosis (TB). Preclinical and clinical data suggest that higher doses of rifampicin, resulting in disproportionally higher systemic exposures to the drug, are more effective. Serum concentrations of rifampicin are the intermediary link between the dose administered and eventual response and only protein-unbound (free) rifampicin is pharmacologically active.