Determination of ciprofloxacin in plasma by micro-liquid chromatography-mass spectrometry: an adapted method for neonates.

There are many limitations to conducting pharmacokinetic studies in neonates, both ethical and technical. Regarding technical aspects, the number and volume of samples are limited, and the analytical method to measure drug concentration should be both specific and highly sensitive. In the present report, an analytical method adapted to neonates was developed for the determination of ciprofloxacin plasma concentration. After a simple protein precipitation, analytes were separated on a micro-liquid chromatography and quantified by mass spectrometry, with D8-ciprofloxacin as internal standard. The calibration range was linear from 25 to 3000 ng/mL. Intra- and inter-day precision was less than 2.4 and 4.1%, respectively. The acceptance criteria of accuracy (between 85 and 115%) were met in all cases. A plasma volume of 150 µL was required to achieve the limit of quantification of 25 ng/mL. The method was successfully applied to routine monitoring of ciprofloxacin in pediatric patients and also used in preclinical studies. It will be used to determine the population pharmacokinetic parameters of ciprofloxacin in neonates.