Simultaneous Liquid Chromatographic Determination of Chloramphenicol and Antiepileptic Drugs (Phenobarbital, Phenytoin, Carbamazepine, and Primidone) in Plasma

Abstract

A method for the simultaneous analysis of chloramphenicol [an antibiotic administered to pediatric patients for the 1st-line treatment of Haemophilus influenzae meningitis] and 4 antiepileptic drugs (phenobarbital, phenytoin, carbamazepine and primidone) in plasma by high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of plasma with diethyl ether containing phenacetin as an internal standard, chromatography with a reversed-phase column with a methanol-water mobile phase and detection by measuring UV absorbance at 210 nm. The method demonstrated sufficient precision, sensitivity and specificity: the recoveries of the drugs were > 95% with the exclusion of primidone (80.3%); the maximum within-day and day-to-day coefficients of variation for all drugs were < 5%; the lower detection limits were .ltoreq. 0.5 .mu.g/ml for all drugs analyzed; and 6 other antibiotics [ampicillin, amoxicillin, penicillin G, tobramycin, moxalactam and amikacin], phenylethylmalondiamide, carbamazepine-10,11-epoxide, and chloramphenicol esters did not interfere with the analysis. The HPLC method was tested for clinical applicability by analyzing plasma samples from a volunteer who received concurrent single doses of chloramphenicol, phenobarbital and phenytoin. This method can be used for studying drug interactions between chloramphenicol and antiepileptic drugs and for monitoring the concentrations of these drugs in plasma when administered concurrently, to prevent concentration-related side effect(s) of each drug.