Abstract
A specific and sensitive radioimmunoassay for the determination of levels of zalcitabine in human plasma, urine, and cerebrospinal fluid has been developed. Commercially available radiolabel and antiserum (Sigma Chemicals) were used after dilution in assay buffer. Prior to the immunoassay, standard and patient samples were subjected to solid-phase extraction on silica columns in order to obtain purified samples. The lower limit of quantitation was determined to be 1 ng/ml. Intra- and interassay variations were less than 11% for a number of quality control samples of drug in plasma and urine. Results from parallelism studies with plasma and urine demonstrated that samples outside the standard range (1 to 30 ng/ml) could be diluted by blank plasma or assay buffer, respectively. A large number of related compounds and potentially coadministered drugs were tested for cross-reactivity. Stability tests showed that heat treatment for 30 min at 60 degrees C or storage for 1 month at -30 degrees C did not affect zalcitabine concentrations in plasma or urine. The radioimmunoassay with solid-phase extraction for sample cleanup discussed here has been successfully applied in a pharmacokinetic study of a single patient, demonstrating its applicability for clinical pharmacokinetic research with zalcitabine.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Burger D. M., Rosing H., Koopman F. J., Mennhorst P. L., Mulder J. W., Bult A., Beijnen J. H. Determination of 3'-amino-3'-deoxythymidine, a cytotoxic metabolite of 3'-azido-3'-deoxythymidine, in human plasma by ion-pair high-performance liquid chromatography. J Chromatogr. 1993 Dec 22;622(2):235–242. doi: 10.1016/0378-4347(93)80271-5. [DOI] [PubMed] [Google Scholar]
- Burger D. M., Rosing H., van Gijn R., Meenhorst P. L., van Tellingen O., Beijnen J. H. Determination of stavudine, a new antiretroviral agent, in human plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 1992 Dec 23;584(2):239–247. doi: 10.1016/0378-4347(92)80581-a. [DOI] [PubMed] [Google Scholar]
- Gustavson L. E., Fukuda E. K., Rubio F. A., Dunton A. W. A pilot study of the bioavailability and pharmacokinetics of 2',3'-dideoxycytidine in patients with AIDS or AIDS-related complex. J Acquir Immune Defic Syndr. 1990;3(1):28–31. [PubMed] [Google Scholar]
- Jajoo H. K., Bennett S. M., Kornhauser D. M. Thermospray liquid chromatographic-mass spectrometric analysis of anti-AIDS nucleosides: quantification of 2',3'-dideoxycytidine in plasma samples. J Chromatogr. 1992 Jun 10;577(2):299–304. doi: 10.1016/0378-4347(92)80251-k. [DOI] [PubMed] [Google Scholar]
- Kalin J. R., Hill D. L. Determination of 2',3'-dideoxyadenosine, 2',3'-dideoxyinosine and 2',3'-dideoxycytidine in biological samples. J Chromatogr. 1988 Sep 23;431(1):184–191. doi: 10.1016/s0378-4347(00)83083-2. [DOI] [PubMed] [Google Scholar]
- Kelley J. A., Litterst C. L., Roth J. S., Vistica D. T., Poplack D. G., Cooney D. A., Nadkarni M., Balis F. M., Broder S., Johns D. G. The disposition and metabolism of 2',3'-dideoxycytidine, an in vitro inhibitor of human T-lymphotrophic virus type III infectivity, in mice and monkeys. Drug Metab Dispos. 1987 Sep-Oct;15(5):595–601. [PubMed] [Google Scholar]
- Klecker R. W., Jr, Collins J. M., Yarchoan R. C., Thomas R., McAtee N., Broder S., Myers C. E. Pharmacokinetics of 2',3'-dideoxycytidine in patients with AIDS and related disorders. J Clin Pharmacol. 1988 Sep;28(9):837–842. doi: 10.1002/j.1552-4604.1988.tb03225.x. [DOI] [PubMed] [Google Scholar]
- Magnani M., Rossi L., Bianchi M., Cucchiarini L., Stocchi V. Reversed-phase liquid chromatographic determination of 2',3'-dideoxycytidine in human blood samples. J Chromatogr. 1989 Jun 30;491(1):215–220. doi: 10.1016/s0378-4347(00)82835-2. [DOI] [PubMed] [Google Scholar]
- Mathes L. E., Muschik G., Demby L., Polas P., Mellini D. W., Issaq H. J., Sams R. High-performance liquid chromatographic determination of 2',3'-dideoxycytidine and 3'-azido-3'-deoxythymidine in plasma using a column-switching technique. J Chromatogr. 1988 Nov 18;432:346–351. doi: 10.1016/s0378-4347(00)80664-7. [DOI] [PubMed] [Google Scholar]
- Morse G. D., Shelton M. J., O'Donnell A. M. Comparative pharmacokinetics of antiviral nucleoside analogues. Clin Pharmacokinet. 1993 Feb;24(2):101–123. doi: 10.2165/00003088-199324020-00002. [DOI] [PubMed] [Google Scholar]
- Qian M. X., Swagler A. R., Mehta M., Vishwanathan C. T., Gallo J. M. Pharmacokinetic evaluation of drug interactions with anti-human immunotrophic virus (HIV) Drugs. III. 2',3'-Dideoxycytidine (ddC) and zidovudine in monkeys. Pharm Res. 1992 Feb;9(2):224–227. doi: 10.1023/a:1018941507979. [DOI] [PubMed] [Google Scholar]
- Rubio F. R., Crews T., Garland W. A., Fukuda E. K. Quantification of dideoxycytidine in human plasma by gas chromatography/mass spectrometry. Biomed Environ Mass Spectrom. 1988 Nov;17(5):399–404. doi: 10.1002/bms.1200170509. [DOI] [PubMed] [Google Scholar]
- Slusher J. T., Kuwahara S. K., Hamzeh F. M., Lewis L. D., Kornhauser D. M., Lietman P. S. Intracellular zidovudine (ZDV) and ZDV phosphates as measured by a validated combined high-pressure liquid chromatography-radioimmunoassay procedure. Antimicrob Agents Chemother. 1992 Nov;36(11):2473–2477. doi: 10.1128/aac.36.11.2473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whittington R., Brogden R. N. Zalcitabine. A review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS). Drugs. 1992 Oct;44(4):656–683. doi: 10.2165/00003495-199244040-00009. [DOI] [PubMed] [Google Scholar]
