Human saliva-based quantitative monitoring of clarithromycin by flow injection chemiluminescence analysis: a pharmacokinetic study

Human saliva quantitative monitoring of clarithromycin (CLA) by chemiluminescence (CL) with flow injection analysis was proposed for the first time, which was based on the quenching effect of CLA on luminol-bovine serum albumin (BSA) CL system with a linear range from 7.5 × 10(-4) to 2.0 ng/ml. This proposed approach, offering a maximum sample throughput of 100 h(-1), was successfully applied to the quantitative monitoring of CLA levels in human saliva during 24 h after a single oral dose of 250 mg intake, with recoveries of 95.2 ∼ 109.0% and relative standard deviations lower than 6.5 % (N = 7). Results showed that CLA reached maximum concentration of 2.28 ± 0.02 μg/ml at approximately 3 h, and the total elimination ratio was 99.6 % in 24 h. The pharmacokinetic parameters including absorption rate constant (0.058 ± 0.006 h(-1)), elimination rate constant (0.149 ± 0.009 h(-1)) and elimination half-life time (4.66 ± 0.08 h) were obtained. A comparison of human saliva and urine monitoring was also given. The mechanism study of BSA-CLA interaction revealed the binding of CLA to BSA is an entropy driven and spontaneous process through hydrophobic interaction, with binding constant K BSA-CLA of 4.78 × 10(6) l/mol and the number of binding sites n of 0.82 by flow injection-chemiluminescence model. Molecular docking analysis further showed CLA might be in subdomain IIA of BSA, with K BSA-CLA of 6.82 × 10(5) l/mol and ΔG of -33.28 kJ/mol.