| A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood. | |
| | |
MedLine Citation:
|
PMID: 20590590 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2)S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H(2)S in blood and tissues. EXPERIMENTAL APPROACH: Concentrations of reactive sulphide in saline and freshly drawn whole blood were quantified by reaction with the thio-specific derivatization agent monobromobimane, followed by reversed-phase fluorescence HPLC and/or mass spectrometry. In pharmacokinetic studies, male rats were exposed either to intravenous infusions of sodium sulphide or to H(2)S gas inhalation, and levels of available blood sulphide were measured. Levels of dissolved H(2)S/HS(-) were concomitantly measured using an amperometric sensor. KEY RESULTS: Monobromobimane was found to rapidly and quantitatively derivatize sulphide in saline or whole blood to yield the stable small molecule sulphide dibimane. Extraction and quantification of this bis-bimane derivative were validated via reversed-phase HPLC separation coupled to fluorescence detection, and also by mass spectrometry. Baseline levels of sulphide in blood were in the range of 0.4-0.9 microM. Intravenous administration of sodium sulphide solution (2-20 mg x kg(-1) x h(-1)) or inhalation of H(2)S gas (50-400 ppm) elevated reactive sulphide in blood in a dose-dependent manner. Each 1 mg x kg(-1) x h(-1) of sodium sulphide infusion into rats was found to be pharmacokinetically equivalent to approximately 30 ppm of H(2)S gas inhalation. CONCLUSIONS AND IMPLICATIONS: The monobromobimane derivatization method is a sensitive and reliable means to measure reactive sulphide species in whole blood. Using this method, we have established a bioequivalence between infused sodium sulphide and inhaled H(2)S gas. |
| | |
Authors:
|
Edward A Wintner; Thomas L Deckwerth; William Langston; Asa Bengtsson; Dina Leviten; Paul Hill; Michael A Insko; Ronald Dumpit; Emily VandenEkart; Christopher F Toombs; Csaba Szabo |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: British journal of pharmacology Volume: 160 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2010 Jun |
Date Detail:
|
Created Date: 2010-07-01 Completed Date: 2010-11-03 Revised Date: 2011-07-28 |
Medline Journal Info:
|
Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
|
Languages: eng Pagination: 941-57 Citation Subset: IM |
Affiliation:
|
Ikaria, Seattle, WA, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Analytic Sample Preparation Methods
/
methods* Animals Bicyclo Compounds / chemistry* Chromatography, High Pressure Liquid Fluorescent Dyes / chemistry Free Radicals / analysis, blood, chemistry Humans Hydrogen Sulfide / administration & dosage, blood, chemistry, pharmacokinetics Kinetics Limit of Detection Male Rats Rats, Sprague-Dawley Spectrometry, Fluorescence Spectrometry, Mass, Electrospray Ionization Sulfhydryl Compounds / analysis, blood*, chemistry Sulfhydryl Reagents / chemistry* Sulfides / administration & dosage, blood*, chemistry, pharmacokinetics*, therapeutic use Tandem Mass Spectrometry |
| Chemical | |
Reg. No./Substance:
|
0/Bicyclo Compounds; 0/Fluorescent Dyes; 0/Free Radicals; 0/Sulfhydryl Compounds; 0/Sulfhydryl Reagents; 0/Sulfides; 1313-82-2/sodium sulfide; 71418-44-5/monobromobimane; 7783-06-4/Hydrogen Sulfide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A novel quinone-based derivative (DTNQ-Pro) induces apoptotic death via modulation of heat shock pro...
Next Document: Simultaneous detection of intracellular target and off-target binding of small molecule cancer drugs...