Analysis of S-35 labeled WR-2721 and its metabolites in biological fluids

Kent W. Anderson, Kenneth Krohn, Zdenka Grunbaum, Roger B. Phillips, Peter A. Mahler, Thomas W. Menard, Alexander M. Spence, Janet S. Rasey

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Studies with WR-2721 and related compounds have been hindered by the lack of a suitable assay for the drug and its major metabolites. We have developed a chromatographic method which requires no derivatization for the separation and detection of WR-2721, the free thiol, its symmetrical disulfide and other mixed disulfides. Our procedure involves ion-pairing for separation of ionizable compounds by causing polar molecules to become more lipophilic and hence separable using reverse phase HPLC. Detection is based upon liquid scintillation counting of S-35 incorporated during the synthesis of the parent compound. This method requires no pre-column preparation of samples and, by detecting the S-35 label, eliminates the chance that a coeluting species could interfere with detection, as might occur with post-column derivatization. Chromatography was done using a 10 micron C8RP column and 35% MeOH/65% 0.0113M NaH2PO4, 0.005 M hexanesulfonate, pH 5.9, flowing at 1 ml/min. Half-minute fractions were collected into scintillation vials for counting. Retention volumes for the various compounds were: column breakthrough (3.5 ml), WR-2721 (4.5 ml), WR-1065 (9 ml), and WR-33278 (24 ml). This analytical technique employing radiotracers can be used to study radioprotective mechanisms by time dependent measurements of the tissue distribution and chemical form of labeled drug. Such chemical information can then be correlated with biological measures of radiation protection.

Original languageEnglish (US)
Pages (from-to)1511-1515
Number of pages5
JournalInternational journal of radiation oncology, biology, physics
Volume10
Issue number9
DOIs
StatePublished - 1984
Externally publishedYes

Fingerprint

Amifostine
metabolites
Scintillation Counting
Disulfides
fluids
disulfides
scintillation
counting
Radiation Protection
drugs
Tissue Distribution
Sulfhydryl Compounds
Pharmaceutical Preparations
Chromatography
radiation protection
chromatography
High Pressure Liquid Chromatography
thiols
Ions
preparation

Keywords

  • Autoradiography
  • Chromatography
  • Metabolites
  • S-35
  • WR-2721

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Analysis of S-35 labeled WR-2721 and its metabolites in biological fluids. / Anderson, Kent W.; Krohn, Kenneth; Grunbaum, Zdenka; Phillips, Roger B.; Mahler, Peter A.; Menard, Thomas W.; Spence, Alexander M.; Rasey, Janet S.

In: International journal of radiation oncology, biology, physics, Vol. 10, No. 9, 1984, p. 1511-1515.

Research output: Contribution to journalArticle

Anderson, KW, Krohn, K, Grunbaum, Z, Phillips, RB, Mahler, PA, Menard, TW, Spence, AM & Rasey, JS 1984, 'Analysis of S-35 labeled WR-2721 and its metabolites in biological fluids', International journal of radiation oncology, biology, physics, vol. 10, no. 9, pp. 1511-1515. https://doi.org/10.1016/0360-3016(84)90492-9
Anderson, Kent W. ; Krohn, Kenneth ; Grunbaum, Zdenka ; Phillips, Roger B. ; Mahler, Peter A. ; Menard, Thomas W. ; Spence, Alexander M. ; Rasey, Janet S. / Analysis of S-35 labeled WR-2721 and its metabolites in biological fluids. In: International journal of radiation oncology, biology, physics. 1984 ; Vol. 10, No. 9. pp. 1511-1515.
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AU - Menard, Thomas W.

AU - Spence, Alexander M.

AU - Rasey, Janet S.

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