Ceftriaxone pharmacokinetics by a sensitive and simple LC-MS/MS method: Development and application.

Ceftriaxone is a third-generation cephalosporin, worldwide use as a first-line treatment for several infections, including life-threatening infections as meningitis or endocarditis. Nowadays, ceftriaxone use is changing, embracing high-dose schemes, new populations treated and requirement of dose individualization and optimization. These reasons warranted the development of new sensitive assays. This study aimed to develop and validate a fast and handy bioanalytical method for the quantification of ceftriaxone in human plasma covering a broad range of concentrations. The analysis was performed using high-performance liquid chromatography coupled to tandem mass spectrometry. Sample preparation was based on protein precipitation with acetonitrile followed by centrifugation. Chromatography separation was performed on Phenomenex Luna C18 column (5 µm, 150 × 2.0 mm) and a mobile phase consisting of 70 % of mobile phase A (10 mM of ammonium acetate and 1% formic acid in purified water) and 30 % mobile phase B (0.1 % formic acid in acetonitrile) at a flow rate of 500 µl/min on an isocratic program. Both the analyte and the internal standard were quantified using the positive electrospray ionization (ESI) mode within a single runtime of 5.00 min. The method was validated following the U.S. Food and Drug Administration guidelines over the concentration range of 3-1000 µg/mL. The within-run and between-run precision and accuracy were <15 %, and therefore met the standard regulatory acceptance criterion. In conclusion, a sensitive and robust LC-MS/MS method was developed for a fast quantitation of ceftriaxone concentrations in plasma samples with multiples applications in research and clinical therapeutic drug monitoring.

Ampicillin and Ceftriaxone Solution Stability at Different Temperatures in Outpatient Parenteral Antimicrobial Therapy.

The inclusion of ampicillin-containing regimens in outpatient parenteral antimicrobial therapy programs (OPAT) depends upon solution stability under conditions similar to those experienced in these programs. Lack of this information could hinder the inclusion in OPAT of patients suffering from Enterococcus faecalis infective endocarditis treated with ampicillin plus ceftriaxone. The purpose of this study is to determine the stability of ampicillin and ampicillin plus ceftriaxone solutions in a simulated outpatient setting conditions. Solutions of ampicillin 24 g/liter and ampicillin 24 g/liter combined with ceftriaxone 8 g/liter were stored at 25°C ± 2°C, 30°C ± 2°C and 37°C ± 2°C for 48 h. Chemical and physical stability were evaluated at 20, 24, 30, and 48 h after manufacturing. The solutions were considered stable if the percentage of intact drug was ≥90% and color and clearness remained unchanged. After 24 h of storage at a controlled temperature, ampicillin solution in 0.9% sodium chloride was found to be stable for 30 h at 25 and 30°C and for 24 h at 37°C. In the ampicillin plus ceftriaxone combined solution, both antibiotics were found to be stable after 30 h of storage at 25 and 30°C, but at 37°C, the stability criterion was not met at any time point. Our study offers solid evidence demonstrating that the concentrations of both drugs at two of the tested temperatures (25°C and 30°C) were stable for up to 30 h. Therefore, both ampicillin alone and ampicillin plus ceftriaxone solutions would be appropriate candidates for inclusion in OPAT programs.