Abstract
Aim: An innovative Atg4B inhibitor, S130, exhibited a negative influence on colorectal cancer cells in vitro and in vivo. To assist reliable toxicodynamic and pharmacokinetic evaluation, an LC–MS/MS assay of S130 in rat plasma must be necessary. Results: An LC–MS/MS assay for determination of S130 in rat plasma has been first developed and fully verified whose values met the admissible limits as per the US FDA guidelines. Chromatographic separation was achieved by using an isocratic elution after 3 min. MS was conducted under the ESI+ mode fitted with selected reaction monitoring. The calibration curve proved acceptable linearity over 0.50–800 ng/ml. Conclusion: The developed LC–MS/MS assay of S130 in rat plasma is easily applicable in pharmacokinetics study and the further toxicological evaluation.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
Reference
- 1. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int. J. Mol. Sci. 18(1), 197 (2017).
- 2. Colorectal cancer: from prevention to personalized medicine. World J. Gastroenterol. 20(22), 6786–6808 (2014).
- 3. . Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years. World J. Gastroenterol. 20(29), 9775–9827 (2014).
- 4. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J. Biol. Chem. 278(6), 3671–3678 (2013).
- 5. Unraveling the roles of Atg4 proteases from autophagy modulation to targeted cancer therapy. Cancer Lett. 373(1), 19–26 (2016). • Reports functions of Atg4 in cancer therapy.
- 6. ATG4B promotes colorectal cancer growth independent of autophagic flux. Autophagy 101(8), 454–465 (2014).
- 7. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors. Autophagy 10(11), 2021–2035 (2014).
- 8. The core autophagy protein ATG4B is a potential biomarker and therapeutic target in CML stem/progenitor cells. Blood 123(23), 3622–3634 (2014).
- 9. Measurement of the activity of the ATG4 cysteine proteases. Methods Enzymol. 587, 207–225 (2017).
- 10. High-throughput fluorescence assay for small-molecule inhibitors of autophagins/Atg4. J. Biomol. Screen 16(2), 174–182 (2011).
- 11. Discovery of fluoromethylketone-based peptidomimetics as covalent ATG4B (autophagin-1) inhibitors. ACS. Med. Chem. Lett. 7(8), 802–806 (2016).
- 12. Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer in vitro and in vivo. Autophagy 20, 1–17 (2018). •• Article of the pharmacodynamics of S130 both in vitro and in vivo.
- 13. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J. Biol. Chem. 278, 3671–3678 (2003).
- 14. US FDA. Guidance for industry (2018): bioanalytical method validation, US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) and Center for Veterinary Medicine (CVM) (2018). www.fda.gov/downloads/drugs/guidances/ucm070107.pdf
- 15. Development, validation, and application of an UPLC–MS/MS method for norvancomycin analysis in human blood plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1072, 199–204 (2018).
- 16. EMA. Guideline on bioanalytical method validation, EMEA/CHMP/EWP/192217/2009. Rev. 1 Corr. 2** Committee for Medicinal Products for Human Use (CHMP) (2011). www.ema.europa.eu/docs/en_GB
- 17. Clinical and Laboratory Standards Institute (CLSI). Mass spectrometry in the clinical laboratory: general principles and guidances; approved guideline, CLSI document C50-A. Wayne, PA, Clinical and Laboratory Standards Institute (2007). https://clsi.org/media/1352/c50a_sample.pdf
- 18. US FDA. Draft guidance for industry (2013): bioanalytical method validation, US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation(CDER) and Research and Center for Veterinary Medicine (CVM) (2013). www.fda.gov/downloads/drugs/guidancesucm368107.pdf
- 19. Pharmacokinetic study of salvianolic acid A in beagle dog after oral administration by a liquid chromatography–mass spectrometry method: a study on bioavailability and dose proportionality. J. Ethnopharmacol. 148(2), 617–623 (2013).
- 20. Multiple-ascending-dose pharmacokinetics and safety evaluation of baicalein chewable tablets in healthy chinese volunteers. Clin. Drug Investig. 36(9), 713–724 (2016).
- 21. Confidence interval criteria for assessment of dose proportionality. Pharm. Res. 17(10),1278–1283 (2000).
- 22. Pharmacokinetics of single-dose sildenafil administered orally in clinically healthy dogs: effect of feeding and dose proportionality. J. Vet. Pharmacol. Ther. 41(3), 457–462 (2018).