Desarrollo y validación de un procedimiento de medida para la medición simultánea de la concentración de masa de ceftazidima, meropenem y piperacilina en el plasma mediante UHPLC-MS/MS

Abstract

IntroductionCeftazidime, meropenem and piperacillin are broad spectrum antibiotics often used for the empirical treatment of infections in critically ill patients with sepsis. These antibiotics show time-dependent antimicrobial activity, meaning that the antibiotic mass concentration in plasma should be measured and maintained above the minimal inhibitory concentration. The aim of this study was to develop and to validate an ultra-performance liquid chromatography-tandem mass spectrometry procedure for the simultaneous measurement of ceftazidime, meropenem, and piperacillin mass concentration in plasma. Material and methodsAfter protein precipitation with acetonitrile and subsequent dilution of the supernatant with water, eluates were introduced into a reverse-phase C18 column using a water/methanol gradient containing formic acid. Antibiotics were detected by electrospray ionisation mass spectrometry in multiple reaction monitoring mode. ResultsThe lower limits of quantification were close to 0.50mg/l. Coefficients of variation and absolute relative biases were less than 10.8 and 12.0%, respectively. Recovery values ranged from 55.7 to 77.4%. Evaluation of the matrix effect showed ion enhancement for all antibiotics. No interferences or carry-over were observed. ConclusionsThe validated measurement procedure could be used in daily clinical laboratory practice to measure the mass concentration of these antibiotics in plasma, and in critically ill patients with sepsis.