High-Performance Liquid Chromatography for Analyses of Antibiotics in Biological Fluids

Abstract

The discovery of penicillin and subsequently other antibiotics represents one of the great progresses in modern medicine. Newer agents, such as the aminoglyco-sides and the cephalosporins, have also contributed significantly to man's struggle against bacterial and fungal infections, and antiviral agents are expected to emerge in the next decades. The evergrowing number of antibiotics have, however, also given rise to several problems. The emergence of bacterial strains resistant to antibiotics is a matter of increasing concern to the medical profession and necessitates the continuing search for new antimicrobial agents and judicious therapy with the ones already in use. Many antibiotics exert undesired toxic side effects when given in excessive doses: examples are the oto-and nephrotoxicity of aminoglycosides, the bone-marrow depressant action of chloramphenicol and the nephrotoxic effects of some of the early cephalosporins. Even a comparatively nontoxic drug such as penicillin causes coma and convulsions at high levels in the cerebrospinal fluid. To avoid such undesired effects it is of vital importance to the clinician to have a clear understanding of the pharmacological behaviour of an antibiotic. Usually, abundant data are available on the pharmacokinetics of these drugs in healthy, young volunteers but these do not represent the clinically difficult cases: the sick, often older, patient many times suffering from reduced renal or hepatic function and the very small child with immature function of liver and kidneys. When treating these patients, the clinician must be able to monitor serum levels of antibiotics to ensure safe and effective theratherapy. Therefore, when a new drug is introduced, it is necessary to perform extensive investigations of pharmacokinetic behaviour not only in healthy volunteers but also in patients with and without disturbances of metabolic pathways and elimination processes in order to make adequate dosage recommendations.