Study of Bioanalytical Methodologies for Amikacin and its Application in Therapeutic Drug Monitoring in Neonates

Abstract

Background: Amikacin belongs to aminoglycosides family, commonly administered newlinein the treatment of systemic infections due to gram negative bacteria. Its narrow newlinetherapeutic index results in adverse effects like nephrotoxicity and ototoxicity. Ultra newlinehigh performance liquid chromatography (UHPLC) based analytical method for the newlinedetermination of amikacin sulfate in human serum using derivatizaon with FMOC-Cl newlineand glycine. Therapeutic drug monitoring in preterm infants requisite due to their newlineextensive pharmacological variability and rapidly evolving physiological newlinedevelopments. newlinePreterm infants are prone to severe infections due to their immature and newlineimmuno-compromised health conditions. The differential body composition and renal newlineimmaturity among preterm infants contributes to enlarge pharmacokinetics inter- newlineindividual variability. Population pharmacokinetic seeks to study and assess patient newlinecharacteristics (age, body weight, drug elimination and distribution and other newlineparameters alter drug PK parameters) extent of variability among the patient newlinepopulation. Aim of POP-PK analysis is the identification of factors and their effects, newlineresponsible for inter- and intra-variability. newlineMethods: Pre-column derivatization reaction of amikacin performed using newlinefluorescence reagent 9-fluorenylmethyl chloroformate (FMOC-Cl) at ambient newlinetemperature in the presence of borate buffer (0.2 M). Stabilizing reagent glycine newline(0.1 M) added into the reaction mixture solution after completion of the derivatization newlinereaction for stabilization of fluorescent complex product. Fluorimetric detection of newlineamikacin was performed at excitation and emission wavelength of 265 nm and 315 newlinenm respectively, using C18 UHPLC column. The reported method was validated by newlineperforming linearity, precision, recovery and ruggedness. newlinexviii newline newlineOne compartment model was used to calculate pharmacokinetics and newlinemodulated amikacin dosage regimen based on obtained amikacin peak and trough newlineconcentration at 3rd dose. Pharmacokinetic data were analyzed