Drug degradation during HPLC analysis of aztreonam: Effect on pharmacokinetic parameter estimation

Lawrence V. Friedrich, Roger L. White, Michael B. Kays, David S. Burgess

    Research output: Contribution to journalArticle

    Abstract

    OBJECTIVE: To assess the impact of degradation of aztreonam, a beta-lactam antibiotic, during HPLC analysis on pharmacokinetic parameter estimates. METHODS: The baseline (B) serum concentration-time data from a published pharmacokinetic study of aztreonam were degraded using first-order equations and a degradation rate constant (0.014 h-1) determined from a preliminary degradation study. Samples were mathematically degraded for autosampler run times of 8–13 h (D1) to approximate a normal work day and for autosampler run times of 16–17 h (D2) and compared with B data. It was assumed that B data were nondegraded and that changes in chromatography were the result of degradation of azetreonam and not to any changes in chromatographic conditions. A two-compartment model was used to fit the data and pharmacokinetic parameters were calculated using standard equations. Statistical significance between all pharmacokinetic parameters for B and D1 and B and D2 was determined using the paired, two-tailed Student’s t-test. RESULTS: Increased variability was noted for all pharmacokinetic parameters for D1 and D2 compared with B. Statistically significant differences were found for clearance (B <D1, p=0.0095 and B <D2, p=0.0194), steady-state volume of distribution (B <D2, p=0.0392), and area under the serum concentration-time curve (B >D1, p=0.0497). CONCLUSIONS: Aztreonam degradation resulted in increased variability in pharmacokinetic parameter estimates. Investigators should be cognizant of this and preliminary studies should be performed to characterize degradation for the length of the expected autosampler run.

    Original languageEnglish (US)
    Pages (from-to)444-446
    Number of pages3
    JournalAnnals of Pharmacotherapy
    Volume28
    Issue number4
    DOIs
    StatePublished - Apr 1994

    ASJC Scopus subject areas

    • Pharmacology (medical)

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