Preclinical assessment of the distribution, metabolism, and excretion of S-propargyl-cysteine, a novel H2S donor, in Sprague-Dawley rats

Abstract

Aim: To study the distribution, metabolism and excretion of S-propargyl-cysteine (SPRC), a novel hydrogen sulfide (H 2 S) donor, after oral administration in rats. Methods: Adult Sprague-Dawley rats were used. The tissue distribution of [35 S] SPRC-derived radioactivity was measured using a liquid scintillation counter. The plasma protein binding of SPRC was examined using 96-well equilibrium dialysis. The excretion of SPRC in urine, bile and feces was analyzed using the LC-MS/MS method. The major metabolites in rat biomatrices were identified using MRM information-dependent, acquisition-enhanced product ion (MRM-IDA-EPI) scans on API 4000QTrap system. Results: After oral administration of [ 35 S] SPRC at a dose of 75 mg/kg, [ 35 S] SPRC-derived radioactivity displayed broad biological distribution in various tissues of rats, including its target organs (heart and brain) with the highest in kidney. On the other hand, the binding of SPRC to human, rat and dog plasma protein was low. Only 2.18%±0.61% and 0.77%±0.61% of the total SPRC administered was excreted unchanged in the bile and urine. However, neither intact SPRC nor its metabolites were detected in rat feces. The major metabolic pathway in vivo (rat bile, urine, and plasma) was N-acetylation. Conclusion: The preliminary results suggest that SPRC possesses acceptable pharmacokinetic properties in rats.

The Pharmacological Effects of S-Propargyl-Cysteine, a Novel Endogenous H2S-Producing Compound

“…LC-MS/MS was used to analyze the excretion of SPRC in urine, bile, and feces, which is 2.18 AE 0.61 %, 0.77 AE 0.61 %, and undetectable, respectively. The major metabolite in rat biomatrices, which was identified by MRM information-dependent, acquisition-enhanced product ion (MRM-IDA-EPI) scans on API 4000 QTRAP system, was N-acetylation (Zheng et al 2012). These pharmacokinetic properties of SPRC were observed similar in previous pharmacokinetic SAC study (Nagae et al 1994;Krause et al 2002).…”

“…The SPRC distribution was measured through stable isotope-labeled technique (Zheng et al 2012 35 S]PRC-derived radioactivity, which exceeded that of plasma. On the other side, several targeted organs, like brain, heart, lung, and intestine, presented lower […”

<p>A Novel Liposomal S-Propargyl-Cysteine: A Sustained Release of Hydrogen Sulfide Reducing Myocardial Fibrosis via TGF-β1/Smad Pathway</p>

“…In spite of this, ZYZ-802 suffers from one major drawback, that of its rapid metabolism and elimination in animal tissues. 26 This fact alone limits any clinical application for this molecule and as such new delivery strategies are needed to improve the pharmacokinetic profile of this molecule. 27 Lately, liposomes have been shown as useful delivery vehicles for drugs with poor physiochemical characteristics like poor solubility or poor pharmacokinetics traits.…”

Pharmacokinetics, protein binding and metabolism of a quinoxaline urea analog as an NF‐κB inhibitor in mice and rats by LC‐MS/MS

“…MRM–information dependent acquisition–enhanced product ion (MRM‐IDA‐EPI) scans were used for the identification of the metabolites, which resulted in the identification of a higher number of metabolites compared with neutral loss (NL), precursor ion (PI), and enhanced mass spectrometry (EMS) scans. The details of our approach in metabolite identification were described previously (Huang et al ., , ; Zheng et al ., ). Briefly, EPI spectra of analytes were collected to identify the three most abundant fragments for each analyte.…”