The presence of lead decreases the availability of meso-2, 3-dimercaptosuccinic acid for analysis in the monobromobimane assay.

The presence of lead decreases the availability of meso-2, 3-dimercaptosuccinic acid for analysis in the monobromobimane assay.
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铅的存在降低了单溴二甲双胍测定中内消旋 2, 3-二巯基丁二酸的可用性。

DOI:
10.1021/tx980247y
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发表时间:
1999
影响因子:
4.1
通讯作者:
Parsons,TL
Parsons,TL
中科院分区:
医学3区
文献类型:
--
作者:
Lever,SZ;Parsons,TL

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meso-2,3-Dimercaptosuccinic acid is a suitable chelating agent for routine pharmacotherapy of lead poisoning in children. Administration ofmeso-2,3-dimercaptosuccinic acid presumably permits complexation of lead in vivo, allowing excretion through urine or feces. Quantification of the lead is achieved independently from the analysis ofmeso-2,3-dimercaptosuccinic acid and metabolites from the monobromobimane assay. To date, no direct chemical characterization of the Pb species excreted in urine has been successful. Pharmacokinetic correlation of lead excretion with excretion ofmeso-2,3-dimercaptosuccinic acid and metabolites has been utilized as an indirect method to draw conclusions regarding the identity of the active chelating agent. In this study, we hypothesized that the Pb-coordinated thiols are not reactive with respect to monobromobimane, and thus, the active chelator contained in the lead complex escapes detection. We performed variations of the assay and found that (1) the fluorescence detector response for themeso-2,3-dimercaptosuccinic acid−monobromobimane adduct was clearly attenuated as a function of added Pb, (2) whenmeso-2,3-dimercaptosuccinic acid and monobromobimane were mixed prior to the addition of lead, the lead had no effect on detector response, (3) the addition of dithiothreitol does not affect the ability of Pb to react withmeso-2,3-dimercaptosuccinic acid and verifies that oxidation ofmeso-DMSA had not occurred, and (4) the addition of ethylenediaminetetraacetic acid to the assay reverses the result found in point 1, presumably through trans chelation of the Pb−DMSA complex. Indirect quantification of the Pb−DMSA complexes found in urine might be accomplished through modification of the standard monobromobimane assay for analysis ofmeso-2,3-dimercaptosuccinic acid.