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Antimicrobial Agents and Chemotherapy, October 2004, p. 3813-3816, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3813-3816.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Liquid Chromatography Assay for Routine Monitoring of Cellular Ribavirin Levels in Blood

Yoichi Inoue,1 Masato Homma,1* Yasushi Matsuzaki,2 Minoru Shibata,3 Takuya Matsumura,3 Takayoshi Ito,3 Keiji Mitamura,3 Naomi Tanaka,2 and Yukinao Kohda1

Department of Pharmaceutical Sciences,1 Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki,2 Second Department of Internal Medicine, Showa University, Shinagawa, Tokyo, Japan3

Received 16 February 2004/ Returned for modification 29 April 2004/ Accepted 29 June 2004

Ribavirin-induced hemolytic anemia is one cause for cessation of combination therapy with alpha interferon 2b and ribavirin for hepatitis C infection. Determining cellular ribavirin levels in blood, including the levels of its phosphorylated metabolites, might be useful for predicting ribavirin-induced anemia, because the metabolites accumulate in erythrocytes. We simplified an assay method developed previously to make it suitable for routine monitoring of cellular ribavirin. Whole blood diluted with a sixfold volume of ice-cold distilled water was subjected to acid phosphatase digestion to convert phosphorylated ribavirin metabolites to free ribavirin. The resulting mixture, spiked with an internal standard, was treated by phenyl boronic acid column extraction, followed by reverse-phase high-performance liquid chromatography analysis. The calibration curve for ribavirin levels in whole blood was linear at concentrations of 5.3 to 1,024 µM (r2 = 0.9999). Validation coefficients of variation for intra- and interday assays were 2.9 to 5.8% and 4.3 to 8.3%, respectively. We tested this method by monitoring blood ribavirin concentrations in two hepatitis C patients receiving alpha interferon 2b-plus-ribavirin combination therapy.

* Corresponding author. Mailing address: Department of Pharmaceutical Sciences, Institute of Clinical Medicine, University of Tsukuba, Ten-nodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan. Phone: 81-298-53-3859. Fax: 81-298-53-7025. E-mail: masatoh{at}md.tsukuba.ac.jp.

Antimicrobial Agents and Chemotherapy, October 2004, p. 3813-3816, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3813-3816.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chan, A. H., Partovi, N., Ensom, M. H. (2009). The Utility of Therapeutic Drug Monitoring for Ribavirin in Patients with Chronic Hepatitis C--A Critical Review. The Annals of Pharmacotherapy 43: 2044-2063 [Abstract] [Full Text]  
  • Morello, J., Rodriguez-Novoa, S., Jimenez-Nacher, I., Soriano, V. (2008). Usefulness of monitoring ribavirin plasma concentrations to improve treatment response in patients with chronic hepatitis C. J Antimicrob Chemother 62: 1174-1180 [Abstract] [Full Text]  


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