High-performance liquid chromatography of 2-mercaptopropionylglycine and its metabolite 2-mercaptopropionic acid in plasma and urine after treatment with thiopronine

Kågedal, Bertil; Andersson, Tommy; Carlsson, Mats; Denneberg, Torsten; Hoppe, Astrid

doi:10.1016/0378-4347(87)80119-6

Cited by 30 publications

(19 citation statements)

References 7 publications

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“…Thus, in plasma a decreasing proportion of non-protein-bound [(a + b)/(a + b + c)] tiopronin was found with time after iv [4] or oral [5] administration, i. e. the relative protein binding of tiopronin increased with time after intake. Once established, the protein-binding of tiopronin in plasma is quite strong, and chemical reduction is required to split the bond and so to release the drug from proteins [1,2]. This is also the case with the disulphide part…”

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confidence: 95%

“…Carlsson, Department of Internal Medicine, University Hospital, S-581 85 Link6ping, Sweden (T-S-S-T and T-S-S-R) of non-protein-bound tiopronin [1,2]. Once the low-molecular weight species of tiopronin have mainly disappeared from plasma, the amount remaining corresponds to protein-bound tiopronin and a (low-molecular weight) fraction released from tissue to plasma.…”

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confidence: 96%

“…This phase is very slow and strong tissue binding may be the reason for the very high (virtual) distribution volume. It should be noted that, due to the presence of a number of molecular species [1,2,4,5], the same time periods should be used when elimination constants are compared [6].…”

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“…From analytical studies [1,2,3], however, and from comparison with other thiols it can be deduced that in biological fluids several molecular species of tiopronin will be found including a) tiopronin as a free thiol (T-SH), the administered form, b)tiopronin as a symmetrical disulphide (T-S-S-T), or as mixed disulphide (T-S-S-R) with another low-molecular thiols (R-SH), such as cysteine and glutathione, and c) tiopronin as mixed disulphide with proteins (T-S-S-P) bearing a free thiolgroup.No method for the analysis of the free thiol (a) in plasma has yet appeared. By our methods [1, 2] we quantify either the sum of low-molecular thiol and disulphides (a + b) -called non-protein-bound or unbound tiopronin -or the sum of all molecular species (a + b + c) -called total tiopronin.…”

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confidence: 99%

“…By our methods [1,2] we quantify either the sum of low-molecular thiol and disulphides (a + b) -called non-protein-bound or unbound tiopronin -or the sum of all molecular species (a + b + c) -called total tiopronin. The urinary tiopronin method [1,2] includes all tiopronin species (a + b + c), but under normal physiological conditions the urinary excretion constitutes only a + b. No method has yet been published for specific analysis of tiopronin in biological tissues.…”

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The pharmacokinetics of tiopronin as such is unknown

Denneberg

et al. 1994

Eur J Clin Pharmacol

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The lack of investigation of the chemical binding of tiopronin to other compounds has hampered our understanding of the drug. From analytical studies [1,2,3], however, and from comparison with other thiols it can be deduced that in biological fluids several molecular species of tiopronin will be found including a) tiopronin as a free thiol (T-SH), the administered form, b)tiopronin as a symmetrical disulphide (T-S-S-T), or as mixed disulphide (T-S-S-R) with another low-molecular thiols (R-SH), such as cysteine and glutathione, and c) tiopronin as mixed disulphide with proteins (T-S-S-P) bearing a free thiolgroup.No method for the analysis of the free thiol (a) in plasma has yet appeared. By our methods [1, 2] we quantify either the sum of low-molecular thiol and disulphides (a + b) -called non-protein-bound or unbound tiopronin -or the sum of all molecular species (a + b + c) -called total tiopronin. The urinary tiopronin method [1, 2] includes all tiopronin species (a + b + c), but under normal physiological conditions the urinary excretion constitutes only a + b. No method has yet been published for specific analysis of tiopronin in biological tissues.Like compounds in other thiol-disulphide systems, the different molecular species of tiopronin can interchange with each other. However, the reaction rates with tiopronin are not known, and understanding of the detailed pharmacokinetics of individual molecular species of tiopronin therefore must await further analytical and chemical studies.It should be understood that the S-S bridge is a covalent bond. Thus, in plasma a decreasing proportion of non-protein-bound [(a + b)/(a + b + c)] tiopronin was found with time after iv [4] or oral [5] administration, i. e. the relative protein binding of tiopronin increased with time after intake. Once established, the protein-binding of tiopronin in plasma is quite strong, and chemical reduction is required to split the bond and so to release the drug from proteins [1,2]. This is also the case with the disulphide part

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confidence: 95%

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confidence: 96%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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The pharmacokinetics of tiopronin as such is unknown

Denneberg

et al. 1994

Eur J Clin Pharmacol

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Chemiluminescent Determination of Tiopronin and its Metabolite, 2-Mercaptopropionic Acid, in Urine by HPLC Coupled with a Flow Injection Set-up

Zhao

Baeyens

Zhang

et al. 1997

Biomed. Chromatogr.

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Chemical Reagents and Derivatization Procedures in Drug Analysis

Danielson¹,

Gallagher²,

Bao³

2000

Encyclopedia of Analytical Chemistry

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This article describes both pre‐ and postcolumn derivatization chemistry used in conjunction with either chromatography or capillary electrophoresis (CE) to facilitate the determination of drugs. Generally, only prederivatization is used in gas chromatography (GC), principallyto enhance the volatility, temperature stability, and/or detectability. The GC section considers derivatization of drugs by reagent class: alkylation, acylation, and silylation. The GC sample handling section describes an approach which combines the extraction and derivatization steps together. Both pre‐ and postcolumn derivatization are common approaches for high‐performance liquid chromatography (HPLC) and many of these methods have been adapted for CE. Derivatization for HPLC is often directed toward aliphatic amines, carboxylic acids, or alcohols that are difficult to detect at low levels by absorbance, luminescence, or electrochemical means. In addition, small hydrophilic molecules upon prederivatization are often converted into larger more hydrophobic compounds, making reversed‐phase HPLC easier or even feasible. The HPLC section considers derivatization of drugs based on type: alkaloids, amines, antibiotics, barbiturates, carbonyl compounds and carboxylic acids, catecholamines, hydroxy compounds, steroids, and sulfur compounds. For the GC and HPLC sections, tables are included giving the structures of the more important derivatizing agents, the analytes, and the corresponding reaction products. A brief rationale for derivatization chemistry with CE concludes this article. For CE, derivatization is often done to improve detectability since the path length for absorbance detection is very short and fluorescence can be effective using laser‐based systems.

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High-performance liquid chromatography of 2-mercaptopropionylglycine and its metabolite 2-mercaptopropionic acid in plasma and urine after treatment with thiopronine

Cited by 30 publications

References 7 publications

The pharmacokinetics of tiopronin as such is unknown

The pharmacokinetics of tiopronin as such is unknown

Chemiluminescent Determination of Tiopronin and its Metabolite, 2-Mercaptopropionic Acid, in Urine by HPLC Coupled with a Flow Injection Set-up

Chemical Reagents and Derivatization Procedures in Drug Analysis

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