Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics
Sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an indication. In this paper, we established and validated a bioanalytical method for the determination of GMDTC in rat plasma, and used i...
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/1191 |
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| author | Wei Hu Zhi-Yong Zhong Yu-Ting Gao Xue-Feng Ren Hai-Yang Liu Xiao-Jiang Tang |
| author_facet | Wei Hu Zhi-Yong Zhong Yu-Ting Gao Xue-Feng Ren Hai-Yang Liu Xiao-Jiang Tang |
| author_sort | Wei Hu |
| collection | DOAJ |
| description | Sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an indication. In this paper, we established and validated a bioanalytical method for the determination of GMDTC in rat plasma, and used it to determine the drug concentrations in the plasma of rats after intravenous dosing in different genders and dosages. After pretreating the plasma samples with an acetonitrile–water–ammonia solution (70:30:1.25, <i>v</i>/<i>v</i>/<i>v</i>), liquid chromatographic separations were efficiently achieved with a XBridge C18 column using a 5 min gradient system of aqueous ammonium bicarbonate and 95% acetonitrile–water solution (95:5, <i>v</i>/<i>v</i>) as the eluent. The GMDTC and metolazone (internal standard, IS) detection were carried out using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (LC–MS/MS), monitored at <i>m</i>/<i>z</i> 390.06–324.1 (for the GMDTC, tR: 2.03 min) and <i>m</i>/<i>z</i> 366.0–259.2 (for IS, tR: 3.88 min). The GMDTC was stable under various testing conditions, and this analytical method conforms to the verification standard of biological analysis methods. The half-life (t<sub>1/2</sub>) was determined to be 0.54–0.65 h for the intravenous, mean distribution volume and clearances were 1.08–2.08 L/kg and 1–3 L/h/kg, respectively. The AUC<sub>0-t</sub> and AUC<sub>0-∞</sub> found after increasing the dosage exhibited a linear relationship with the administered dose. There were no statistically significant differences in the values obtained for the different genders at dosages of 50, 100 and 250 mg/kg, respectively (<i>p</i> > 0.05). This is the first report of a bioanalytical method to quantify GMDTC in rat plasma using LC–MS/MS, which provides useful information for the study of its pharmacological effects and clinical applications. |
| first_indexed | 2024-03-11T09:33:12Z |
| format | Article |
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| spelling | doaj.art-3af11532ac9b44249353f1e973e1c1772023-11-16T17:28:58ZengMDPI AGMolecules1420-30492023-01-01283119110.3390/molecules28031191Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical PharmacokineticsWei Hu0Zhi-Yong Zhong1Yu-Ting Gao2Xue-Feng Ren3Hai-Yang Liu4Xiao-Jiang Tang5Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, ChinaJianersheng (Zhuhai) Pharmtech Co., Ltd., Zhuhai 519040, ChinaJianersheng (Zhuhai) Pharmtech Co., Ltd., Zhuhai 519040, ChinaJianersheng (Zhuhai) Pharmtech Co., Ltd., Zhuhai 519040, ChinaKey Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, ChinaJianersheng (Zhuhai) Pharmtech Co., Ltd., Zhuhai 519040, ChinaSodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an indication. In this paper, we established and validated a bioanalytical method for the determination of GMDTC in rat plasma, and used it to determine the drug concentrations in the plasma of rats after intravenous dosing in different genders and dosages. After pretreating the plasma samples with an acetonitrile–water–ammonia solution (70:30:1.25, <i>v</i>/<i>v</i>/<i>v</i>), liquid chromatographic separations were efficiently achieved with a XBridge C18 column using a 5 min gradient system of aqueous ammonium bicarbonate and 95% acetonitrile–water solution (95:5, <i>v</i>/<i>v</i>) as the eluent. The GMDTC and metolazone (internal standard, IS) detection were carried out using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (LC–MS/MS), monitored at <i>m</i>/<i>z</i> 390.06–324.1 (for the GMDTC, tR: 2.03 min) and <i>m</i>/<i>z</i> 366.0–259.2 (for IS, tR: 3.88 min). The GMDTC was stable under various testing conditions, and this analytical method conforms to the verification standard of biological analysis methods. The half-life (t<sub>1/2</sub>) was determined to be 0.54–0.65 h for the intravenous, mean distribution volume and clearances were 1.08–2.08 L/kg and 1–3 L/h/kg, respectively. The AUC<sub>0-t</sub> and AUC<sub>0-∞</sub> found after increasing the dosage exhibited a linear relationship with the administered dose. There were no statistically significant differences in the values obtained for the different genders at dosages of 50, 100 and 250 mg/kg, respectively (<i>p</i> > 0.05). This is the first report of a bioanalytical method to quantify GMDTC in rat plasma using LC–MS/MS, which provides useful information for the study of its pharmacological effects and clinical applications.https://www.mdpi.com/1420-3049/28/3/1191GMDTCcadmiumpharmacokineticLC–MS/MSbioanalytical method |
| spellingShingle | Wei Hu Zhi-Yong Zhong Yu-Ting Gao Xue-Feng Ren Hai-Yang Liu Xiao-Jiang Tang Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics Molecules GMDTC cadmium pharmacokinetic LC–MS/MS bioanalytical method |
| title | Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics |
| title_full | Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics |
| title_fullStr | Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics |
| title_full_unstemmed | Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics |
| title_short | Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics |
| title_sort | establishment of lc ms ms method for determination of gmdtc in rat plasma and its application in preclinical pharmacokinetics |
| topic | GMDTC cadmium pharmacokinetic LC–MS/MS bioanalytical method |
| url | https://www.mdpi.com/1420-3049/28/3/1191 |
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