Direct infusion nano-electrospray ionization mass spectrometry for therapeutic drug monitoring of ciprofloxacin and its metabolites in human saliva.

A rapid and sensitive method based on direct infusion-nano-electrospray ionization mass spectrometry (DI-nESI-MS) has been developed for the detection and quantification of ciprofloxacin and its metabolites in human saliva. Saliva samples were collected after the oral administration of 500 mg ciprofloxacin tablets. Internal standard (IS), tamoxifen, was added to the collected samples, and then diluted with the ionization solvent, centrifuged and filtered. An aliquot of 4 μL of the filtrate was loaded into a nanospray (NS) capillary. The NS capillary was then fitted into an off-line ion source and the instrument was operated to acquire a two-minute run by applying a voltage of 1000 V (positive-ion detection mode). Quantification of ciprofloxacin relied on the ratio of its peak intensity to the IS peak intensity. The DI-nESI-MS method was validated and provided satisfactory precision with relative standard deviation ranging from 0.39 to 7.48 % and accuracy with relative error ranging from -2.12 to 9.72 %. The calibration curve showed good linearity (r) > 0.999 over the concentration range of 10-4000 ng/mL. These results verify the effectiveness of the DI-nESI-MS method for monitoring of ciprofloxacin and its metabolites in human saliva samples.