Thermospray liquid-chromatography mass spectrometry of thiol radioprotective agents: Characteristics spectra. Scientific report

Technical Report · Fri Jan 01 04:00:00 EST 1988

OSTI ID:5631041

Walden, T L; Buchner, J; Pizzitola, V; Blakeley, W F

Ethiofos (S-2(3-aminopropylamino)ethylphosphorothioic acid or WR-2721) is currently being evaluated in clinical radiotherapy trials (Kligerman et al., 1980) because of its potential for enhancing the efficacy of radiotherapy (Kligerman et al., 1980; Yuhas and Storer, 1969). For proper drug usage and pharmacological studies, it is necessary to assess the stability of the aminothiol and the presence of impurities or decomposition products. In addition, monitoring the plasma levels of WR-2721 and its metabolites should improve the therapeutic usefulness of WR-2721. Several high-performance liquid chromatography (HPLC) methodologies have been developed that are applicable for routine analysis of aminothiols and endogeneous cellular thiols (Newton et al., 1981; Swynnerton et al., 1984). One of these methodologies, electrochemical detection, permits the simultaneous detection of the free thiol and the disulfides (Swynnerton et al. 1984). Mass spectrometry (MS) is a sensitive technique that can confirm purity and provide useful structural information. Using a thermospray interface, samples can be introduced into the mass spectrometer from a liquid chromatograph (LC) (Vestal, 1984). The interface thermally nebulizes the eluant into a high-pressure region of the mass spectrometer where a variety of soft-ionization techniques may be used to ionize the analyte molecules. The feasibility of LC coupled to MS-detection was studied for the analysis of thiol-containing radioprotective agents, including glutathione, WR-2721, and WR-1065, the dephosphorylated sulfhydryl form of WR-2721, which has been shown to be its active radioprotective metabolite (Calabro-Jones et al., 1983).

• Research Organization: Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)
• OSTI ID: 5631041
• Report Number(s): AD-A-207917/6/XAB; AFRRI-SR-89-13
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
CHEMICAL ANALYSIS
CHEMISTRY
CHROMATOGRAPHY
DETECTION
DOCUMENT TYPES
DRUGS
ELECTROCHEMISTRY
FLUIDS
GLUTATHIONE
HIGH PRESSURE
IMPURITIES
IONIZATION
LIQUID COLUMN CHROMATOGRAPHY
LIQUIDS
MEDICINE
METABOLITES
MOLECULES
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
PHARMACOLOGY
POLYPEPTIDES
PROGRESS REPORT
PROTEINS
RADIOLOGY
RADIOPROTECTIVE SUBSTANCES
RADIOTHERAPY
SENSITIVITY
SEPARATION PROCESSES
THERAPY
THIOLS