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Updated: Aug 6, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Analysis for penicillins and cefoperazone by HPLC-photolysis-electrochemical detection (HPLC-hv-EC)
C M Selavka1, I S Krull, K Bratin
1The Barnett Institute of Chemical Analysis and Department of Chemistry, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
Abstract:
Continuous, post-column, on-line, real-time photolytic derivatization or degradation can now be used following HPLC separation of various penicillin derivatives prior to conventional thin-layer, amperometric electrochemical detection using oxidative working potentials. Beta-lactam derivatives are separated by conventional reversed-phase HPLC, and each separated penicillin is then photolytically degraded to form, it is presumed, stable anionic species, which are then conveyed to the on-line electrochemical detector for qualitative and quantitative determinations. These methods of trace drug analysis have been applied to four separate penicillins or prodrugs, as well as one typical cephalosporin, viz. cefoperazone. Analytical parameters of the analysis have been determined, including dual electrode response ratios, sensitivity, minimum detection limits, linearity of calibration plots and the range of linear calibration. Finally, the analysis of cefoperazone-spiked saline solutions for i.v. administration has been performed in a single-blind study, as well as the determination of bacampicillin HCl in formulations obtained from a drug manufacturer in the United States. The overall method of analysis for these drugs has been demonstrated as being reproducible, accurate, and precise for at least five beta-lactam analogs. It is suggested that other beta-lactams will be amenable to these newer methods of analysis in a wide variety of sample matrices, including solid or liquid formulations, aqueous infusion solutions, and biological media, such as blood and urine.
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