Measurement of ceftazidime concentration in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry. Application to critically ill patients and patients with osteoarticular infections

Abstract

Ceftazidime is an antibiotic belonging to the third generation of the cephalosporin family. It is indicated in the treatment of serious, simple or mixed bacterial infections, and its administration in continuous or intermittent infusion allows optimization of the concentration of antibiotic to keep it above the minimum inhibitory concentration. We developed and validated a chromatographic method by ultra-performance liquid chromatography-tandem mass spectrometry to measure ceftazidime concentration in human plasma. Following extraction with acetonitrile and 1,2-dichloroethane, the chromatographic separation was achieved using an Acquity ® UPLC ® BEH(TM) (2.1 × 100 mm i.d., 1.7 µm) reverse-phase C18 column, with a water-acetonitrile linear gradient containing 0.1% formic acid at a 0.4 mL/min flow rate. Ceftazidime and its internal standard (cefotaxime) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge transitions of 547.0 → 467.9/396.1 and 456.0 → 395.8/324.1, respectively. The limit of quantification was 0.58 mg/L and linearity was observed in the range 0.58-160 mg/L. Coefficients of variation and absolute relative biases were <9.8 and 8.4%. The mean recovery for ceftazidime was 74.4 ± 8.1%. Evaluation of the matrix effect showed ion enhancement, and no carry-over was observed. The validated method could be applied to daily clinical laboratory practice to measure the concentration of ceftazidime in plasma.

Monitoring of cefepime in human serum and plasma by micellar electrokinetic capillary chromatography: Improvement of sample preparation and validation by liquid chromatography coupled to mass spectrometry

“…Corresponding values for ceftazidime were 71.3 and 73.9%, respectively. The matrix effect defined as the ratio of peak area response in presence of matrix and absence of matrix components was 1.1 in all cases. The limit for quantitation was taken as 0.25 μg/mL (smallest calibrator) and the detection limit was determined to be 0.1 μg/mL (S/N = 3).…”

Preanalytical Stability of Flucloxacillin, Piperacillin, Tazobactam, Meropenem, Cefalexin, Cefazolin, and Ceftazidime in Therapeutic Drug Monitoring: A Structured Review

“…Fifteen published articles included data on the preanalytical stability of ceftazidime. 9,10,15–19,26–28,32,36,52–54 These data are shown in Figure 1F. At room temperature, ceftazidime has been reported to be stable for 8 hours in several studies.…”

“…At 2–8°C, ceftazidime has been reported to be stable for at least 3 days in several studies. 10,17,19,53 One study found instability at 2–8°C after 3 days, 52 which conflicts with the finding of stability for up to 6 days reported in another study. 19 At −20°C, ceftazidime has been reported to be stable for at least 3 weeks.…”

24/7 Therapeutic Drug Monitoring of Beta-Lactam Antibiotics with CLAM-2000

“…In addition, both antibiotics were stable for 6 h after storage at room temperature for 4 h followed by storage at 4 • C after gel separation [12]. Similarly, ceftazidime and flucloxacillin were stable in plasma for 12 h, both at 4 • C on the autosampler and at room temperature (RT) [12,13,47]. Meropenem was stable for 8 h at 4 • C and 3-6 h at RT in both whole blood and plasma, while piperacillin was stable for 48 h in plasma without gel separation [40].…”