Abstract
The use of high-performance liquid chromatography (HPLC) to measure ribavirin in serum and other biological fluids has been limited by endogenous interfering substances. We report an HPLC procedure based on the extraction of ribavirin from serum, plasma, or cerebrospinal fluid with a boronate affinity gel, which uses a 3-methylcytidine internal standard. This assay is sensitive (to 0.4 microM), specific (no interference with 34 commonly prescribed drugs), reproducible (coefficients of variation from 5.4 to 22.4%), and linear (r = 0.999) over the range of clinically relevant concentrations in serum (from 0.5 to 50.0 microM). It also correlates well with the ribavirin radioimmunoassay (r = 0.992). This HPLC assay should be useful for measuring ribavirin in serum and other body fluids during clinical trials.
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Selected References
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- Austin R. K., Trefts P. E., Hintz M., Connor J. D., Kagnoff M. F. Sensitive radioimmunoassay for the broad-spectrum antiviral agent ribavirin. Antimicrob Agents Chemother. 1983 Nov;24(5):696–701. doi: 10.1128/aac.24.5.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chandrasekaran B., Ardalan B. High-performance liquid chromatographic determination of 2-beta-D-ribofuranosylthiazole-4-carboxamide in urine and plasma. J Chromatogr. 1983 Aug 12;276(1):237–242. doi: 10.1016/s0378-4347(00)85089-6. [DOI] [PubMed] [Google Scholar]
- Crumpacker C., Heagy W., Bubley G., Monroe J. E., Finberg R., Hussey S., Schnipper L., Lucey D., Lee T. H., McLane M. F. Ribavirin treatment of the acquired immunodeficiency syndrome (AIDS) and the acquired-immunodeficiency-syndrome-related complex (ARC). A phase 1 study shows transient clinical improvement associated with suppression of the human immunodeficiency virus and enhanced lymphocyte proliferation. Ann Intern Med. 1987 Nov;107(5):664–674. doi: 10.7326/0003-4819-107-5-664. [DOI] [PubMed] [Google Scholar]
- Davis G. E., Suits R. D., Kuo K. C., Gehrke C. W., Waalkes T. P., Borek E. High-performance liquid chromatographic separation and quantitation of nucleosides in urine and some other biological fluids. Clin Chem. 1977 Aug;23(8):1427–1435. [PubMed] [Google Scholar]
- Gilbert B. E., Wilson S. Z., Knight V., Couch R. B., Quarles J. M., Dure L., Hayes N., Willis G. Ribavirin small-particle aerosol treatment of infections caused by influenza virus strains A/Victoria/7/83 (H1N1) and B/Texas/1/84. Antimicrob Agents Chemother. 1985 Mar;27(3):309–313. doi: 10.1128/aac.27.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall C. B., McBride J. T., Walsh E. E., Bell D. M., Gala C. L., Hildreth S., Ten Eyck L. G., Hall W. J. Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. A randomized double-blind study. N Engl J Med. 1983 Jun 16;308(24):1443–1447. doi: 10.1056/NEJM198306163082403. [DOI] [PubMed] [Google Scholar]
- Kirsi J. J., North J. A., McKernan P. A., Murray B. K., Canonico P. G., Huggins J. W., Srivastava P. C., Robins R. K. Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent. Antimicrob Agents Chemother. 1983 Sep;24(3):353–361. doi: 10.1128/aac.24.3.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laskin O. L., Longstreth J. A., Hart C. C., Scavuzzo D., Kalman C. M., Connor J. D., Roberts R. B. Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome. Clin Pharmacol Ther. 1987 May;41(5):546–555. doi: 10.1038/clpt.1987.70. [DOI] [PubMed] [Google Scholar]
- McCormick J. B., King I. J., Webb P. A., Scribner C. L., Craven R. B., Johnson K. M., Elliott L. H., Belmont-Williams R. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986 Jan 2;314(1):20–26. doi: 10.1056/NEJM198601023140104. [DOI] [PubMed] [Google Scholar]
- Pfadenhauer E. H., Tong S. D. Determination of inosine and adenosine in human plasma using high-performance liquid chromatography and a boronate affinity gel. J Chromatogr. 1979 Apr 11;162(4):585–590. doi: 10.1016/s0378-4347(00)81838-1. [DOI] [PubMed] [Google Scholar]
- Prusiner P., Sundaralingam M. A new class of synthetic nucleoside analogues with broad-spectrum antiviral properties. Nat New Biol. 1973 Jul 25;244(134):116–118. doi: 10.1038/newbio244116a0. [DOI] [PubMed] [Google Scholar]
- Roberts R. B., Laskin O. L., Laurence J., Scavuzzo D., Murray H. W., Kim Y. T., Connor J. D. Ribavirin pharmacodynamics in high-risk patients for acquired immunodeficiency syndrome. Clin Pharmacol Ther. 1987 Oct;42(4):365–373. doi: 10.1038/clpt.1987.165. [DOI] [PubMed] [Google Scholar]
- Roboz J., Suzuki R. Determination of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole) in blood and urine by chemical ionization-mass fragmentography. J Chromatogr. 1978 Oct 11;160(1):169–179. doi: 10.1016/s0021-9673(00)91793-x. [DOI] [PubMed] [Google Scholar]
- Rodriguez W. J., Kim H. W., Brandt C. D., Fink R. J., Getson P. R., Arrobio J., Murphy T. M., McCarthy V., Parrott R. H. Aerosolized ribavirin in the treatment of patients with respiratory syncytial virus disease. Pediatr Infect Dis J. 1987 Feb;6(2):159–163. doi: 10.1097/00006454-198702000-00004. [DOI] [PubMed] [Google Scholar]
- Sidwell R. W., Huffman J. H., Khare G. P., Allen L. B., Witkowski J. T., Robins R. K. Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science. 1972 Aug 25;177(4050):705–706. doi: 10.1126/science.177.4050.705. [DOI] [PubMed] [Google Scholar]
- Smee D. F., Sidwell R. W., Barnett B. B., Spendlove R. S. Bioassay system for determining ribavirin levels in human serum and urine. Chemotherapy. 1981;27(1):1–11. doi: 10.1159/000237948. [DOI] [PubMed] [Google Scholar]
- Smith R. H., Gilbert B. E. Quantification of ribavirin in biological fluids and tissues by high-performance liquid chromatography. J Chromatogr. 1987 Feb 20;414(1):202–210. doi: 10.1016/0378-4347(87)80042-7. [DOI] [PubMed] [Google Scholar]
- Westgard J. O., Hunt M. R. Use and interpretation of common statistical tests in method-comparison studies. Clin Chem. 1973 Jan;19(1):49–57. [PubMed] [Google Scholar]
