Pharmacokinetic profile of N-acetylcysteine amide and its main metabolite in mice using new analytical method
| Autor: | Wenyi Zheng, Ying Zhao, Tobias Ginman, Håkan Ottosson, Rui He, Svante Norgren, Moustapha Hassan |
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| Rok vydání: | 2019 |
| Předmět: |
Metabolite
Pharmaceutical Science Biological Availability 02 engineering and technology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Liquid chromatography–mass spectrometry Animals Humans Prodrugs Sulfhydryl Compounds Derivatization chemistry.chemical_classification Mice Inbred BALB C Chromatography Chemistry Prodrug 021001 nanoscience & nanotechnology Glutathione Bioavailability Acetylcysteine NACA Thiol Female 0210 nano-technology |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 143 |
| ISSN: | 1879-0720 |
| Popis: | N-acetylcysteine amide (NACA) is the amide derivative of N-acetylcysteine (NAC) that is rapidly converted to NAC after systemic administration. It has emerged as a promising thiol antioxidant for multiple indications; however, the pharmacokinetic property is yet unclear due to lack of an accurate quantification method. The present investigation aimed to develop an analytical method for simultaneous quantification of NACA and NAC in plasma. A new reagent (2-(methylsulfonyl)-5-phenyl-1,3,4-oxadiazole, MPOZ) was introduced for thiol stabilization during sample processing and storage. Further, we utilized tris (2-carboxyethyl) phosphine (TCEP) to reduce the oxidized forms of NACA and NAC. After derivatization, NACA-MPOZ and NAC-MPOZ were quantified using liquid chromatography–mass spectrometry (LC-MS). The new method was validated and found to have high specificity, linearity, accuracy, precision, and recovery for the quantification of NACA and NAC in plasma. Furthermore, the formed derivatives of NACA and NAC were stable for 48 h under different conditions. The method was utilized in pharmacokinetic study which showed that the bioavailability of NACA is significantly higher than NAC (67% and 15%, respectively). The pharmacokinetic of NACA obeyed a two-compartment open model. The glutathione (GSH)-replenishing capacity was found to be three to four-fold higher after the administration of NACA compared to that observed after the administration of NAC. In conclusion, the present method is simple, robust and reproducible, and can be utilized in both experimental and clinical studies. NACA might be considered as a prodrug for NAC. Furthermore, this is the first report describing the pharmacokinetics and bioavailability of NACA in mouse. |
| Databáze: | OpenAIRE |
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