Penicillamine disulfide

Russell and Rabenstein [43] described a speciation and quantitation method for underivatized and derivatized penicillamine, and its disulfide, by capillary electrophoresis. Penicillamine and penicillamine disulfide were determined by capillary electrophoresis on a capillary (24 cm x 25 pm i.d. or 50 cm x 50 pm i.d. for underivatized thiols) with detection at 357 nm (200 nm for underivatized thiols). The run buffer solution was 0.1 M phosphate (pH 2.3). Detection limits were 20-90 pM without derivatization, and 5-50 pM after derivatization. Calibration graphs were linear from 1 pM to 5 mM thiols. 

Rabenstein and Yamashita [52] determined penicillamine and its symmetrical and mixed disulfides by HPLC in biological fluids. Plasma and urine were deproteinized with trichloroacetic acid, and HPLC was performed on a column (25 cm x 4.6 mm) or Biophase ODS (5 pm) with a mobile phase comprising 0.1 M phosphate buffer (pH 3) and 0.34 mM Na octylsulfate at 1 mL/min. Detection was with a dual Hg-Au amalgam electrode versus a Ag-AgCl reference electrode. (z>)-penicillamine and homocysteine were determined at the downstream electrode at +0.15 V, and homocystine, penicillamine-homocysteine, and penicillamine disulfides were first reduced... 

Pectic acids metal complexes, 984 Penicillamine disulfide... 

Experimentally, the capacity of the D-penicillamine group to act as antigenic determinant has been shown by Assem and Vickers (1974), immunizing rabbits with penicillamine-disulfide protein conjugates. The immunogenicity of D-penicillamine itself, as used for treatment of Wilson s disease or in rheumatic disorders, has been demonstrated (Amos 1973), It has also been shown that penicillamine can behave as experimental contact sensitizer in guinea pigs (Levine 1960 a Caron 1963). 

Disulfides can be reduced chemically, electrochemically or enzymatically. Chemical reduction is often used prior to derivatisation of thiols to fluorophores, but it can also be used with HPLC-ED. Common reducing agents are mercapto-ethanol, DTT, dithioerythritol, cyanide and sodium borohydride, but their efficiency varies towards different disulfides. Cyanide or borohydride rapidly reduce cystine at room temperature, but require over 24 h to reduce cysteine-D-penicillamine disulfide completely, whilst the sterically hindered D-penicillamine disulfide is not reduced at all. ... 

A yield of 89% for D-penicillamine from its homodisulfide using a 10-fold excess of DTT at 60 °C (4 h) has been claimed. Comparative studies with cysteine-D-penicillamine disulfide or protein-bound D-penicillamine were not reported. Kelly et al. reduced cysteamine disulfides and protein-cysteamine with DTT prior to HPLC-ED. However, excess DTT can produce analytical problems since both DTT and its oxidised form are readily separated by RPLC and can be detected electrochemically. 

G.T. Yamashita and D.L. Rabenstein, Determination of penicillamine, penicillamine disulfide and penicillamine-glutathione mixed disulfide by high-performance liquid-chromatography with electrochemical detection, J. Chromatogr. B, 1989,491,341-354. 

The radiochemlstty of the drugs themselves is of interest. Thiyl radicals formed by the radiolysis of cysteine, M A, and the related disulfides in aqueous solution can build up a steady-state concentration and "scramble" many disulfide groups.The radlolysls of aqueous mixtures of cystine and penicillamine disulfide gave a spectrum of products very similar to that obtained from the mixed disulfide of the two components. Cystine alone gave sulfonic acids, while penicillamine difulside, which is not radioprotective, gave none. Perhaps the ability to form sulfonic acids is characteristic of protective disulfides.68... 

Penicillamine U Penicillamine disulfide, penicillamine-cysteine disulfide T H... 

Dithiobis(D-2"amino-3-methvlbutanoic acid) (penicillamine disulfide" H2L... 

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