A fast and high-sensitivity liquid chromatography-tandem mass spectrometry method combined with in vivo microdialysis for quantification of meropenem in rabbits with sepsis under the simultaneous infusion of total parenteral nutrition: Application to a pharmacokinetic study.

A fast and high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) method assisted by microdialysis was established for the determination of meropenem in total parenteral nutrition (TPN) infused plasma. A 10-times dilution was arranged for sample preparation to overcome the severe matrix effect caused by the high salt content in dialysate and complex composition of TPN. This quantification method was proved to be satisfied in selectivity, accuracy, precision, linearity (R2  > 0.998), recovery, matrix effect and stability. In the optimized conditions, the calibration curve range was set from 2 to 2000 ng/ml. This validated method was applied to pharmacokinetics study of meropenem in rabbits with sepsis (induced by cecal ligation and punctures) under simultaneous infusion of TPN to simulate the clinical practice. The results demonstrated that the LC-MS/MS method assisted by microdialysis can be used successfully for the determination of meropenem in TPN-infused plasma. Moreover, the area under the curve and the maximum concentrations in the plasma of meropenem in control rabbits were significantly smaller (P < 0.05), while clearance and distribution volumes were significantly greater (P < 0.05) than in those with sepsis. It could be speculated that drug monitoring in patients with sepsis may be necessary.