Quantification of the carbapenem antibiotic ertapenem in human plasma by a validated liquid chromatography–mass spectrometry method

BackgroundErtapenem (Invanz®) is a newly developed carbapenem β-lactam antibiotic. LC–MS is the method of choice for therapeutic drug monitoring (TDM) of a variety of drugs including antibiotics. No validated LC–MS method for ertapenem quantification is described in the literature so far.MethodsA rapid and robust LC–MS quantification method for ertapenem was developed and validated for clinical routine application in plasma samples. After immediate stabilisation with MES buffer (pH 6.5), samples were prepared for LC–MS analysis using simple protein precipitation. LC–MS coupling was realised by the use of a Phenomenex® Synergi 4μ Polar-RP A80 Mercury LC column (10 × 2.0 mm) in combination with a Single-MS (Agilent 1100 LC–MSD SL) operating in negative selected ion monitoring (SIM) detection mode with ceftazidime as internal standard for adequate selective and sensitive analysis.ResultsLC–MS method validation by means of determination of limit of detection (LOD 0.1 μg mL− 1), lower limit of quantification (LLOQ 1 μg mL− 1), linearity (0.1–50 μg mL– 1), recovery (> 90%), intra- and inter-day precision (RSD < 10%), accuracy (> 90%), inter-subject variability (< 10% at LLOQ), drug stability in plasma (> 3 months) and in post-extracted samples (> 99% for 24 h), and matrix effects (process efficiency > 90%) showed excellent performance parameters considering Guidance for Industry — Bioanalytical Method Validation.ConclusionThis method is perfectly appropriate for routine quantification of ertapenem and possibly other polar carbapenem β-lactam antibiotics.