An improved HPLC assay for S-2-(3-aminopropylamino)ethyl phosphorothioate (WR-2721) in plasma

Swynnerton, Nollie F.; McGovern, Edward P.; Niño, Joe A.; Mangold, Donald J.

doi:10.1016/0360-3016(84)90494-2

Cited by 15 publications

(2 citation statements)

References 1 publication

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“…Thiol prodrugs of conventional xenobiotics and peptide mimetic compounds have been prepared via a thioesterification, phosphorylation, or disulfide formation. These prodrugs are biologically converted to the parent thiol, thus restoring the pharmacological effect of the drug entity (30)(31)(32). Similar chemical modifications may be applied to polypeptides, improve the aqueous solubility or minimize oxidative degradation of polypeptides.…”

Section: Improvement Of the Physicochemical Properties Of Polypeptidementioning

confidence: 99%

Prodrugs of Peptides and Proteins for Improved Formulation and Delivery

Oliyai¹,

Stella²

1993

Annu. Rev. Pharmacol. Toxicol.

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Section: Improvement Of the Physicochemical Properties Of Polypeptidementioning

confidence: 99%

Prodrugs of Peptides and Proteins for Improved Formulation and Delivery

Oliyai¹,

Stella²

1993

Annu. Rev. Pharmacol. Toxicol.

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“…Several methods have been reported for the analysis of amifostine, including HPLC. Swynnerton et al (1984) used precolumn derivatization with¯uorescamine with a total chromatography time of approximately 50 min. Anderson et al (1984) reported a method which does not require any derivatization.…”

mentioning

confidence: 99%

HPLC Analysis of Amifostine

Mandal¹,

Womack²

1999

Pharmacy and Pharmacology Communications

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A simple, rapid HPLC method was developed for the routine analysis of amifostine during formulation development. Chromatography was performed on a μBondapak C‐18 column using a mobile phase of 5 mM heptanesulphonic acid and 5% acetonitrile in 0.1 M chloroacetic acid (pH 3.0) at a flow rate of 1.2 mL min−1 using electrochemical detection (Hg/Au electrode). Retention times for amifostine and WR‐149846, the internal standard, were 4.1 and 5.8 min, respectively. The limit of detection was 0.5 μg mL−1 amifostine. Intra‐ and interday precision coefficients of variation were 1.2–4.9% and 2.3–4.9%, respectively. A maximum variation in the values of slopes of several standard curves was 3.9%. The analysis time for each sample was less than 6 min. As the number of samples required for analysis during the formulation development process is high, this method should significantly reduce the total analysis time.

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Characterization of ethiofos absorption in the rat small intestine

Geary

Swynnerton

Timmons

et al. 1991

Biopharm & Drug Disp

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The absorption characteristics of ethiofos were studied using the rat in situ intestine circulating perfusion technique. Slow absorption kinetics were observed for ethiofos with varying rates of absorption and metabolism/degradation in situ as a function of buffer and absorption enhancers. In most cases less than 10 per cent of the radiolabeled compound is lost from the circulating perfusate in 90 min. In addition, over the same time period greater than 40 per cent of the intact parent compound was lost by degradation. Much of the difference can be accounted for in the formation of the free thiol metabolite. WR-1065, suggesting ester hydrolysis or metabolic activity. Good stability was observed in all perfusate systems ex vivo indicating that the degradation occurs in situ. The disodium salt of ethylenediaminetetraacetic acid (EDTA) was shown to be an effective absorption enhancer of ethiofos. The enhancement of intestinal absorption by EDTA was dose-dependent resulting in a 20-fold increase in blood levels of ethiofos in the portal blood. Follow-up studies in the rhesus monkey confirm this observation. Salicylate and dimethylsulfoxide (DMSO) also resulted in absorption enhancement although to a lesser degree than that seen after EDTA treatment. Addition of several alkaline phosphatase inhibitors did not significantly improve absorption of ethiofos in the rat small intestine. Proposed mechanism(s) for intestinal absorption and absorption enhancement of ethiofos are discussed.

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An improved HPLC assay for S-2-(3-aminopropylamino)ethyl phosphorothioate (WR-2721) in plasma

Cited by 15 publications

References 1 publication

Prodrugs of Peptides and Proteins for Improved Formulation and Delivery

Prodrugs of Peptides and Proteins for Improved Formulation and Delivery

HPLC Analysis of Amifostine

Characterization of ethiofos absorption in the rat small intestine

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