Development of a liquid chromatography–tandem mass spectrometry assay of six antimicrobials in plasma for pharmacokinetic studies in premature infants

This method provides a simple extraction procedure, as well as a validated, sensitive, and specific liquid chromatography–tandem mass spectrometry assay for the simultaneous quantification of ampicillin, piperacillin, tazobactam, meropenem, acyclovir, and metronidazole in human plasma. The method was validated over concentration ranges specific for each compound, with a lower limit of quantification of 50–300 ng/mL and a sample volume of 50 μL. The method is accurate and precise, with within- and between-day accuracy ranging from 85 to 110% and 92 to 110%, respectively, and within- and between-day precision of 89–111% and 91–109%, respectively. Simplicity, low plasma volume, and high throughput make this method suitable for clinical pharmacokinetic studies in premature infants.

► The majority of premature infants receive multiple antimicrobials simultaneously.
► PK sampling in these infants with limited blood volume is challenging.
► Our method successfully quantified 6 antimicrobials simultaneously in human plasma.
► Our method has many applications to pediatric research using micro-volume samples.