Abstract
A sensitive and specific fluorometric high-pressure liquid chromatography technique was developed to measure both tobramycin and an internal standard (gentamicin C2). The assay utilizes direct extraction of the o-phthalaldehyde derivatives from serum and urine. Coefficients of variation were 7.9% (serum) and 6.0% (urine) at a tobramycin concentration of 1.0 microgram/ml. The lower limit of assay sensitivity was 0.2 microgram/ml. Results obtained from high-pressure liquid chromatography were in excellent agreement with those from radioimmunoassay for both serum (r = 0.97) and urine (r = 0.91). No other aminoglycoside antibiotics and no other antibiotics that were tested caused interfering peaks. Tobramycin (1 mg/kg intravenous bolus) was administered to three healthy volunteers. Tobramycin concentrations were detectable for 10 h in serum and for 240 h in urine after a 1-mg/kg intravenous dose. A two-compartment pharmacokinetic model was required to describe the tobramycin disposition. Urinary recovery of tobramycin over a 10-day period accounted for 95.8, 94.3, and 83.1% of the administered dose. High-pressure liquid chromatography methodology is sufficiently sensitive to determine single-dose, two-compartment tobramycin pharmacokinetics from urinary excretion data, thus verifying the prolonged excretion of tobramycin after a single dose. The analytical methodology and pharmacokinetic techniques described may be useful in studying other aminoglycosides.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anhalt J. P. Assay of gentamicin in serum by high-pressure liquid chromatography. Antimicrob Agents Chemother. 1977 Apr;11(4):651–655. doi: 10.1128/aac.11.4.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anhalt J. P., Brown S. D. High-performance liquid-chromatographic assay of aminoglycoside antibiotics in serum. Clin Chem. 1978 Nov;24(11):1940–1947. [PubMed] [Google Scholar]
- Bendush C. L., Weber R. Tobramycin sulfate: a summary of worldwide experience from clinical trials. J Infect Dis. 1976 Aug;134 (Suppl):S219–S234. doi: 10.1093/infdis/134.supplement_1.s219. [DOI] [PubMed] [Google Scholar]
- Hewitt W. L. Gentamicin: toxicity in perspective. Postgrad Med J. 1974 Nov;50 (Suppl 7):55–61. [PubMed] [Google Scholar]
- Maitra S. K., Yoshikawa T. T., Hansen J. L., Nilsson-Ehle I., Palin W. J., Schotz M. C., Guze L. B. Serum gentamicin assay by high-performance liquid chromatography. Clin Chem. 1977 Dec;23(12):2275–2278. [PubMed] [Google Scholar]
- Maitra S. K., Yoshikawa T. T., Steyn C. M., Guze L. B., Schotz M. C. Amikacin assay in serum by high-performance liquid chromatography. Antimicrob Agents Chemother. 1978 Dec;14(6):880–885. doi: 10.1128/aac.14.6.880. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peng G. W., Jackson G. G., Chiou W. L. High-pressure liquid chromatographic assay of netilmicin in plasma. Antimicrob Agents Chemother. 1977 Dec;12(6):707–709. doi: 10.1128/aac.12.6.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schentag J. J., Cumbo T. J., Jusko W. J., Plaut M. E. Gentamicin tissue accumulation and nephrotoxic reactions. JAMA. 1978 Nov 3;240(19):2067–2069. [PubMed] [Google Scholar]
- Schentag J. J., Jusko W. J., Plaut M. E., Cumbo T. J., Vance J. W., Abrutyn E. Tissue persistence of gentamicin in man. JAMA. 1977 Jul 25;238(4):327–329. [PubMed] [Google Scholar]
- Schentag J. J., Lasezkay G., Cumbo T. J., Plaut M. E., Jusko W. J. Accumulation pharmacokinetics of tobramycin. Antimicrob Agents Chemother. 1978 Apr;13(4):649–656. doi: 10.1128/aac.13.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]