| Quantitative determination of acetylshikonin in macaque monkey blood by LC-ESI-MS/MS after precolumn derivatization with 2-mercaptoethanol and its application in pharmacokinetic study | |
| Alternative Title | Quantitative determination of acetylshikonin in macaque monkey blood by LC-ESI-MS/MS after precolumn derivatization with 2-mercaptoethanol and its application in pharmacokinetic study |
| Sun Dongxiao1; Tian Huifang1; Meng Zhiyun1; Du Alicia3; Yuan Dan2; Gu Ruolan2; Wu Zhuona2; Dou Guifang1 | |
| 2008 | |
| Source Publication | ACTA PHARMACOLOGICA SINICA
 |
| ISSN | 1671-4083 |
| Volume | 29Issue:12Pages:1499-1506 |
| Abstract | Aim: To develop and validate a novel precolumn derivatization method for the quantitative determination and pharmacokinetic application of acetylshikonin in macaque monkeys by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Methods: 2-Mercaptoethanol was added to the blood sample as the derivatization reagent. The derivatization reaction formed I major derivation product, which was well correlated with acetylshikonin. The acetylshikonin concentrations in the biological samples were calculated by quantitative determination of the major derivation product using LC-ESI-MS/MS. Separation was achieved using a C-18 column (2 mmx50 nm, 5 mu m) at room temperature and a linear gradient elution with a mobile phase containing methanol (1.96% acetic acid) and 10% methanol in water (1.96% acetic acid and 10 mmol/L ammonium acetate) at a flow rate of 0.2 mL/min. In addition, the major derivative, named derivative III, was identified by UV spectra, MS, and the H-1-NMR and C-13-NMR spectra. Results: Good linearity was obtained within the range of 5 and 2000 ng/mL (r>0.99 using a linear regression model with 1/x(2) weighting) for acetylshikonin. The interday and intraday precisions were found to be less than 12.3%, with the exception of the lowest concentration, which was less than 17.2%. The interday and intraday accuracies, which were between -3% and 0.6%, were also observed. After the administration of acetylshikonin (80 mg/kg, po) in macaque monkeys, the pharmacokinetic parameters were obtained through the non-compartmental analysis, where the area under the concentration-time curve to the last measurable concentration, the terminal elimination half-life, and the mean residual time were 615.4 +/- 206.5 ng.h/mL, 12.3 +/- 1.6 h, and 10.2 +/- 0.7 h, respectively. Conclusion: The method was validated and applied to the quantitative determination and pharmacokinetic study of acetylshikonin in the blood samples of macaque monkeys. |
| Other Abstract | Aim: To develop and validate a novel precolumn derivatization method for the quantitative determination and pharmacokinetic application of acetylshikonin in macaque monkeys by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Methods: 2-Mercaptoethanol was added to the blood sample as the derivatization reagent. The derivatization reaction formed 1 major derivation product, which was well correlated with acetylshikonin. The acetylshikonin concentrations in the biological samples were calculated by quantitative determination of the major derivation product using LC-ESI-MS/MS. Separation was achieved using a C_(18) column (2 mm×50 mm, 5 μm) at room temperature and a linear gradient elution with a mobile phase containing methanol (1.96% acetic acid) and 10% methanol in water (1.96% acetic acid and 10 mmol/L ammonium acetate) at a flow rate of 0.2 mL/min. In addition, the major derivative, named derivative III, was identified by UV spectra, MS, and the ~1H-NMR and ~(13)C-NMR spectra. Results: Good linearity was obtained within the range of 5 and 2000 ng/mL (r>0.99 using a linear regression model with 1/x~2 weighting) for acetylshikonin. The interday and intraday precisions were found to be less than 12.3%, with the exception of the lowest concentration, which was less than 17.2%. The interday and intraday accuracies, which were between _3% and 0.6%, were also observed. After the administration of acetylshikonin (80 mg/kg, po) in macaque monkeys, the pharmacokinetic parameters were obtained through the non-compartmental analysis, where the area under the concentration-time curve to the last measurable concentration, the terminal elimination half-life, and the mean residual time were 615.4±206.5 ng·h/mL,12.3±1.6 h, and 10.2±0.7 h, respectively. Conclusion: The method was validated and applied to the quantitative determination and pharmacokinetic study of acetylshikonin in the blood samples of macaque monkeys. |
| Keyword | SHIKONIN DERIVATIVES CHEMISTRY ALKANNIN BIOLOGY acetylshikonin macaque monkey blood liquid chromatography-electrospray ionization tandem mass spectrometry 2-mercaptoethanol precolumn derivatization pharmacokinetic |
| Indexed By | CSCD |
| Language | 英语 |
| Funding Project | [Beijing Jin BenCao Chinese Herbal Medicine Technology Development] |
| CSCD ID | CSCD:3430175 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.imr.ac.cn/handle/321006/152362 |
| Collection | 中国科学院金属研究所 |
| Affiliation | 1.Beijing Institute Transfus Med, Lab Drug Metab & Pharmacokinet, Beijing 100850, Peoples R China 2.中国科学院金属研究所 3.ThermoFisher Science, San Jose, CA USA |
| Recommended Citation GB/T 7714 | Sun Dongxiao,Tian Huifang,Meng Zhiyun,et al. Quantitative determination of acetylshikonin in macaque monkey blood by LC-ESI-MS/MS after precolumn derivatization with 2-mercaptoethanol and its application in pharmacokinetic study[J]. ACTA PHARMACOLOGICA SINICA,2008,29(12):1499-1506. |
| APA | Sun Dongxiao.,Tian Huifang.,Meng Zhiyun.,Du Alicia.,Yuan Dan.,...&Dou Guifang.(2008).Quantitative determination of acetylshikonin in macaque monkey blood by LC-ESI-MS/MS after precolumn derivatization with 2-mercaptoethanol and its application in pharmacokinetic study.ACTA PHARMACOLOGICA SINICA,29(12),1499-1506. |
| MLA | Sun Dongxiao,et al."Quantitative determination of acetylshikonin in macaque monkey blood by LC-ESI-MS/MS after precolumn derivatization with 2-mercaptoethanol and its application in pharmacokinetic study".ACTA PHARMACOLOGICA SINICA 29.12(2008):1499-1506. |
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