Skip to main content
SpringerLink
Log in

Study on the thermal decomposition of capecitabine

  • Published:
Journal of Thermal Analysis and Calorimetry Aims and scope Submit manuscript

Abstract

The thermal decomposition of capecitabine (CAP) was measured with thermogravimetry, differential scanning calorimetry, and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy. The IR spectra, high-performance liquid chromatography, and liquid chromatography–mass spectrometry of CAP and the residue of its thermal decomposition at various temperatures were determined. The molecular bond orders were calculated using an ab initio method from the GAMESS program of quantum chemistry. The mode of thermal decomposition for CAP was discussed. The kinetic parameters for thermal decomposition such as activation energy E a and the pre-exponential factor A were obtained using the Ozawa method. The prospective lifetime of CAP was estimated using the Dakin equation. The results indicated that the thermal decomposition of CAP is a three-step process, and the first mass loss stage is to lose pentyl formate. The initial decomposition temperature in either nitrogen or air is 120 °C. For decomposition in nitrogen, the E a and A for the initial thermal decomposition are 105.1 kJ mol−1 and 9.12 × 1011 min−1, respectively. For decomposition in air, the corresponding E a and A are 105.1 kJ mol−1 and 9.55 × 1011 min−1, respectively. The CAP has poor thermal stability under routine temperature.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Scheme 2

Similar content being viewed by others

References

  1. Rossi S, editors. Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. 2013.

  2. Cunningham D, Coleman R. New options for outpatient chemotherapy the role of oral fluoropyrimidines. Cancer Treat Rev. 2001;27:211–20.

    Article  CAS  Google Scholar 

  3. Leonard R, Hennessy BT, Blum JL, O’Shaughnessy J. Dose-adjusting capecitabine minimizes adverse effects while maintaining efficacy: a retrospective review of capecitabine for metastatic breast cancer. Clin Breast Cancer. 2011;11(6):349–56.

    Article  CAS  Google Scholar 

  4. Sharma SP. Capecitabine and irinotecan in advanced gastric cancer. Lancet Oncol. 2007;8(7):577.

    Article  Google Scholar 

  5. Li B, Yan J, Zhou T, Wang Z, Li H, Sun H. A phase I study of concurrent late course accelerated hyper-fractionated radiotherapy and capecitabine and cisplatin for local advanced esophageal cancer. Int J Radiat Oncol. 2008;72(1):S283.

    Article  Google Scholar 

  6. Shimma N, Umeda I, Arasaki M, Murasaki C, Masubichi K, Kohchi Y, Miwa M, Ura M, Sawada N, Tahara H, Kuruma I, Horii I, Ishitsuka H. The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine. Bioorg Med Chem. 2000;8(7):1697–706.

    Article  CAS  Google Scholar 

  7. Tao YT, Zhan D, Zhang KL. Kinetics of thermal decomposition of racecadotril in air. Acta Chim Sin. 2006;64(5):435–8 (in Chinese).

    CAS  Google Scholar 

  8. Zhang J, Sheng RL, Mai WP. Studies on the thermal decomposition process and kinetics of purine drugs. Acta Pharm Sin. 2002;3(7–8):644–8 (in Chinese).

    Google Scholar 

  9. Wang XJ, You JZ. Thermal decomposition mechanism and kinetics of stavudine. Chin J Appl Chem. 2011;28(6):709–15 (in Chinese).

    CAS  Google Scholar 

  10. Rompay JV. Purity determination and evaluation of new drug substances. J Pharm Biomed Anal. 1986;4:725–32.

    Article  Google Scholar 

  11. Giron D, Goldbronn C. Use of DSC and TG for identification and quantification of the dosage form. J Therm Anal. 1997;48:473–83.

    Article  CAS  Google Scholar 

  12. Silva ACM, Ga´lico DA, Guerra RB, Perpe´tuo GL, Legendre AO, Rinaldo D, Bannach G. Thermal stability and thermal decomposition of the antihypertensive drug amlodipine besylate. J Therm Anal Calorim. 2015;120:889–92.

    Article  CAS  Google Scholar 

  13. Łaszcz M, Trzcińska K, Filip K, Szyprowska A, Mucha M, Krzeczyński P. Stability studies of capecitabine. J Therm Anal Calorim. 2011;105:1015–21.

    Article  Google Scholar 

  14. Davoudi ET, Noordin MI, Javar HA, Kadivar A, Ashjari M, Chermahini SH. Stability study of the gastric floating dosage form of capecitabine. J Therm Anal Calorim. 2014;115:2495–9.

    Article  CAS  Google Scholar 

  15. Schmidt MW, Baldridge KK, Boatz JA, Elbert ST, Gordon MS, Jensen JJ, Koseki S, Matsunaga N, Nguyen KA, Su S, Windus TL, Dupuis M, Montgomery JA. General atomic and molecular electronic structure system. J Comput Chem. 1993;14:1347–63.

    Article  CAS  Google Scholar 

  16. Alexeev Y, Mazanetz MP, Ichihara O, Fedorov DG. GAMESS as a free quantum-mechanical platform for drug research. Curr Top Med Chem. 2012;12(18):2013–33.

    Article  CAS  Google Scholar 

  17. American Society for Testing and Materials. ASTM E1641-99. 1999. http://www.astm.org/DATABASE.CART/HISTORICAL/E1641-99.htm.

  18. Ozawa T. A new method of analyzing thermogravimetric data. Bull Chem Soc Jpn. 1965;38:1881–6.

    Article  CAS  Google Scholar 

  19. Flynn JH, Wall LA. A quick direct method for the determination of activation energy from thermogravimetric data. J Polym Sci B. 1966;4:323–8.

    Article  CAS  Google Scholar 

  20. The United States Pharmacopeial Convention. Capecitabine. The 35th revision of the United States Pharmacopeia/National Formulary (USP 35-NF30). Washington, 2011;2469–71.

  21. Xie JX, Chang JB, Wang XM. Applications of infrared spectroscopy in organic chemistry and medicinal chemistry. Beijing: Science Press; 2001 (in Chinese).

    Google Scholar 

  22. NIST Chemistry Webbook Standard Reference Database, 2011, 69 release. http://webbook.nist.gov/chemistry

  23. Fulias A, Vlase G, Grigorie C, Ledet¸i I, Albu P, Bilanin M, Vlase T. Thermal behaviour studies of procaine and benzocaine part 1: kinetic analysis of the active substances under non-isothermal conditions. J Therm Anal Calorim. 2013;113:265–71.

    Article  CAS  Google Scholar 

  24. Amorim PHO, Ferreira APG, Machado LCM, Cervini P, Cavalheiro ETG. Investigation on the thermal behavior of b-blockers antihypertensives atenolol and nadolol using TG/DTG, DTA, DSC, and TG–FTIR. J Therm Anal Calorim. 2015;120:1035–42.

    Article  CAS  Google Scholar 

  25. Dakin TW. Electrical insulation deterioration treated as a chemical rate phenomena. AIEE Trans Part I Commun Electron. 1948;67:113–22.

    Google Scholar 

  26. Zhang LJ, Pang JX, Bai JH. Thermogravimetry study of the lifetime of azithromycin. J Hebei NormaI Univ (Nat Sci Ed). 2001;25(4):488–9 (in Chinese).

    CAS  Google Scholar 

Download references

Acknowledgements

This study was financially supported by Zhejiang Provincial Government of China (No. 2011C11032) and Zhejiang International Studies University (No. 07029005).

Author information

Authors and Affiliations

  1. School of Science and Technology, Zhejiang International Studies University, Hangzhou, 310012, China

    Xue-jie Wang & Jin-zong You

Authors
  1. Xue-jie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-zong You
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xue-jie Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Xj., You, Jz. Study on the thermal decomposition of capecitabine. J Therm Anal Calorim 123, 2485–2497 (2016). https://doi.org/10.1007/s10973-015-4857-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10973-015-4857-9

Keywords

Search

Navigation