Determination of S-propargyl-cysteine in rat plasma by mixed-mode reversed-phase and cation-exchange HPLC–MS/MS method and its application to pharmacokinetic studies

Zheng, Yuanting; Liu, Hongrui; Ma, Guoyi; Yang, Ping; Zhang, Lin; Gu, Yi; Zhu, Qing; Shao, Tengfei; Zhang, Peng; Zhu, Yizhun; Cai, Weimin

doi:10.1016/j.jpba.2010.11.027

Cited by 14 publications

(13 citation statements)

References 11 publications

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“…These cysteine derivatives were all bioavailable and were absorbed rapidly and easily in the gastrointestinal tract [15] . After oral administration, […”

Section: Discussionmentioning

confidence: 99%

“…SPRC concentrations were quantitated using the LC-MS/MS method. The analytical method has been previously validated and reported for determining the concentration of SPRC in rat plasma [15] . .…”

Section: Analytical Methods For Sprcmentioning

confidence: 99%

“…Unfavorable pharmacokinetic properties may lead to drug toxicity, potentially resulting in termination of the program or re-optimization of the chemical structure. Previous studies showed that SPRC was rapidly absorbed and bioavailable in rats [15] . Further studies characterizing the disposition of SPRC in vivo are needed to clarify its pharmacokinetic properties.…”

Section: Introductionmentioning

confidence: 96%

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

Zheng

Zhu

et al. 2012

Acta Pharmacol Sin

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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.

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“…These cysteine derivatives were all bioavailable and were absorbed rapidly and easily in the gastrointestinal tract [15] . After oral administration, […”

Section: Discussionmentioning

confidence: 99%

Section: Analytical Methods For Sprcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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

Zheng

Zhu

et al. 2012

Acta Pharmacol Sin

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“…Inhibition studies were conducted as described above with the additional CSE inhibitor PAG (473 μM). The consumption of SPRC and CTT was measured according to the literature4950.…”

Section: Methodsmentioning

confidence: 99%

New method for quantification of gasotransmitter hydrogen sulfide in biological matrices by LC-MS/MS

Tan

Jin

Sun

et al. 2017

Sci Rep

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Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method.

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“…ZYZ-802 was extracted from the plasma samples and measured using LC-MS/MS as previously reported. 36 In brief, chromatographic analysis was performed on an Agilent 1200 Series HPLC system (Agilent Technologies, Palo Alto, CA, USA) equipped with a column (150mm×4.6mm i.d. with 5 µm particles, Shiseido, Japan) which contained C18 bonded silica particles and sulfonic acid cation-exchange particles.…”

Section: Pharmacokinetic Studiesmentioning

confidence: 99%

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

Tran

Chang

et al. 2019

IJN

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S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H 2 S concentrations with known cardioprotective and antiinflammatory effects. However, its rapid metabolism and excretion have limited its clinical application. To overcome these issues, we have developed some novel liposomal carriers to deliver ZYZ-802 to cells and tissues and have characterized their physicochemical, morphological and pharmacological properties. Methods: Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H 2 S concentrations. Using an in vivo model of heart failure (HF), the cardio-protective effects of liposomal carrier were determined by echocardiography, histopathology, Western blot and the assessment of antioxidant and myocardial fibrosis markers. Results: Both liposomal formulations improved ZYZ-802 pharmacokinetics and optimized H 2 S concentrations in plasma and tissues. Liposomal ZYZ-802 showed enhanced cardioprotective effects in vivo. Importantly, liposomal ZYZ-802 could inhibit myocardial fibrosis via the inhibition of the TGF-β1/Smad signaling pathway. Conclusion: The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H 2 S within tissues.

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Determination of S-propargyl-cysteine in rat plasma by mixed-mode reversed-phase and cation-exchange HPLC–MS/MS method and its application to pharmacokinetic studies

Cited by 14 publications

References 11 publications

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

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

New method for quantification of gasotransmitter hydrogen sulfide in biological matrices by LC-MS/MS

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

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