Skip to main content
SpringerLink
Log in

Development of Stability Indicating Methods

  • Chapter
Handbook of Stability Testing in Pharmaceutical Development

Abstract

The evaluation of the chemical stability studies of small molecule pharmaceuticals rely primarily on the availability of a chromatographic or other separation assay capable of separating and quantifying major impurities and degradation products. A staged approach to the development of stability-indicating HPLC methods, consistent with current regulatory guidelines, is outlined. Practical recommendations are provided for developing forced degradation protocols at every stage of drug development and avoiding common pitfalls that may confuse data interpretation. Consideration is given to special cases such as stereoisomeric drugs, polymorphs, and combination drug products.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Smela M J (2005) Regulatory considerations for stability indicating analytical methods in drug substance and drug product testing. Am Pharm Rev 8:51–54.

    Google Scholar 

  2. ICH Q5 (1996) Stability testing of biotechnological/biological products.

    Google Scholar 

  3. ICH Q1A (2003) Stability testing of new drug substances and products.

    Google Scholar 

  4. ICH Q1E (2003) Evaluation of stability data.

    Google Scholar 

  5. ICH Q3A (R) (2003) Impurities in new drug substances.

    Google Scholar 

  6. ICH Q3B (R) (2003) Impurities in new drug products.

    Google Scholar 

  7. ICH Q6A (2000) Guidance on specifications: test procedures and acceptance criteria for new drug substance and products: chemical substances.

    Google Scholar 

  8. ICH Q2A (R) (1995) Guideline for industry, text on validation of analytical procedures.

    Google Scholar 

  9. ICH Q2B (R) (1996) Guideline on validation of analytical procedures: methodology.

    Google Scholar 

  10. Reynolds DW, Facchine KL, Mullaney JF, Alsante KM, Hatajik TD, Motto MG (2002) Available guidance and best practices for conducting forced degradation studies. Pharm Technol 26:48–56.

    Google Scholar 

  11. Reynolds DW (2004) Forced degradation of pharmaceuticals. Am Pharm Rev 7:56–61

    Google Scholar 

  12. Thatcher SR, Mansfield RK, Miller RB, Davis CW, Baertschi SW (2001) Pharmaceutical photostability: a technical guide and practical interpretation of the ICH guideline and its application to pharmaceutical stability – Part I. Pharm Technol N Am 25:98–110.

    CAS  Google Scholar 

  13. Baertschi SW (2005) Pharmaceutical stress testing: predicting drug degradation. Taylor & Francis, Boca Raton.

    Google Scholar 

  14. FDA (2003) Guidance for industry INDs for phase 2 and 3 studies; chemistry, manufacturing, and control information. http://www.fda.gov/CDER/guidance/3619fnl.pdf.

  15. Alsante KM, Martin L, Baertschi SW (2003) A stress testing benchmarking study. Pharm Technol 27:60–72.

    CAS  Google Scholar 

  16. Kats M (2005) Forced degradation studies: regulatory considerations and implementation. BioPharm Int 18:7.

    Google Scholar 

  17. Alsante KM, Ando A, Brown R, Ensing J, Hatajika TD, Kong W, Tsuda Y (2007) The role of degradant profiling in active pharmaceutical ingredients and drug products. Adv Drug Deliv Rev 59:29–37.

    Article  CAS  PubMed  Google Scholar 

  18. Dolan JW (2002) Stability-indicating assays. LCGC N Am 20:346–349.

    CAS  Google Scholar 

  19. Ruan J, Tattersall P, Lozano R, Shah P (2006) The role of forced degradation studies in stability indicating HPLC method development. Am Pharm Rev 9:46–53.

    CAS  Google Scholar 

  20. Wen C (2006) Designing HPLC methods for stability indication and forced degradation samples for API. Am Pharm Rev 9:137–140.

    CAS  Google Scholar 

  21. Baertschi SW, Boccardi G (2005) Oxidative susceptibility testing. In: Baertschi SW (ed) Pharmaceutical stress testing: predicting drug degradation. Taylor & Francis, Boca Raton.

    Google Scholar 

  22. Yoshioka S, Stella VJ (2000) Stability of drugs and dosage forms. Kluwer Academic/Plenum Publishers, New York.

    Google Scholar 

  23. Stepensky D, Chorny M, Dabour Z, Schumacher I (2004) Long-term stability study of L-adrenaline injections: kinetics of sulfonation and racemization pathways of drug degradation. J Pharm Sci 93:969–980.

    Article  CAS  PubMed  Google Scholar 

  24. Ali I, Gupta VK, Aboul-Enein HY (2007) Role of racemization in optically active drugs development. Chirality 19:453–463.

    Article  CAS  PubMed  Google Scholar 

  25. FDA (2007) Guidance for industry ANDAs: pharmaceutical solid polymorphism chemistry, manufacturing, and controls information. http://www.fda.gov/CDER/guidance/7590fnl.pdf.

  26. Donato EM, Dias CL, Rossi RC, Valente RS, Fröelich PE, Bergold AM (2006) LC method for studies on the stability of lopinavir and ritonavir in soft gelatin capsules. Chromatographia 63:437–443.

    Article  CAS  Google Scholar 

  27. Storms ML, Stewart JT (2002) Stability-indicating HPLC assays for the determination of prolocaine and procaine drug combinations. J Pharm Biomed Anal 30:49–52.

    Article  CAS  PubMed  Google Scholar 

  28. Mohammadi A, Rezanour N, Ansari Dogaheh M, Ghorbani Bidkorbeh F, Hashem M, Walker RB (2007) A stability-indicating high performance liquid chromatographic (HPLC) assay for the simultaneous determination of atorvastatin and amlodipine in commercial tablets. J Chromatogr B 846:215–221.

    Article  CAS  Google Scholar 

  29. Hou S, Hindle M, Byron P (2001) A stability-indicating HPLC assay method for budesonide. J Pharm Biomed Anal 24:371–380.

    Article  CAS  PubMed  Google Scholar 

  30. Bashki M, Singh S (2002) Development of validated stability-indicating assay methods-critical review. J Pharm Biomed Anal 28:1011–1040.

    Article  Google Scholar 

  31. Hewitt EF, Lukulay P, Galushko S (2006) Implementation of a rapid and automated high performance liquid chromatography method development strategy for pharmaceutical drug candidates. J Chromatogr A, 1107:79–87.

    Article  CAS  PubMed  Google Scholar 

  32. Brittain H (1974–2006) Analytical profiles of drug substances and excipients (vol 1 to 33), Elsevier, Amsterdam.

    Google Scholar 

  33. Xu Q, Trissel L (2003) Stability-indicating HPLC methods for drug analysis. Pharmaceutical Press, London.

    Google Scholar 

  34. Pasha K, Muzeeb S, Basha SJS, Shashikumar D, Mullangi R, Srinivas NR (2006) Analysis of five HMG-Coa reductase inhibitors-atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin : pharmacological, pharmacokinetic and analytical overview and development of a new method for use in pharmaceutical formulations analysis and in vitro metabolism studies. Biomed Chromatogr 20:282–293.

    Article  CAS  PubMed  Google Scholar 

  35. Snyder L, Kirkland J, Glajch J (1997) Practical HPLC method development. Wiley-Interscience, New York.

    Google Scholar 

  36. Ohannesian L, Streeter A (2002) Handbook of pharmaceutical analysis. Marcel Dekker, New York and Dong M (2006) Modern HPLC for practicing Scientists. John Wiley and Sons, Hoboken.

    Google Scholar 

  37. Karcher BD, Davies ML, Venit JJ, and Delaney EJ (2004) Multi-dimensional screening and analysis (MDSA): an automated tool for HPLC. Am Pharm Rev 7:62–65.

    CAS  Google Scholar 

  38. Bashki M, Singh S (2004) ICH guidance in practice: establishment of inherent stability of secnidazole and development of a validated stability-indicating high-performance liquid chromatographic assay method. J Pharm Biomed Anal 36:769–775.

    Article  Google Scholar 

  39. Cameron G, Jackson PE, Gorenstein MV (1993) A new approach to peak purity assessment using photodiode array detection. Chem Aus, 288–289.

    Google Scholar 

  40. Bryant DK, Kingswood MD, Belenguer A (1996) Determination of liquid chromatographic peak purity by electrospray ionization mass spectrometry. J Chromatogr A 721:41–51.

    Article  CAS  Google Scholar 

  41. Xiao KP, Xiong Y, Liu FZ, Rustum AM (2007) Efficient method development strategy for challenging separations of pharmaceutical molecules using advanced chromatographic technologies. J Chromatogr A, 1163:145–156.

    Article  CAS  PubMed  Google Scholar 

  42. Polite L (2000) Liquid chromatography: basic overview. In: Miller J, Crowther JB (eds) Analytical chemistry in a GMP environment: a practical guide. John Wiley & Sons, New York.

    Google Scholar 

  43. Burana-Osot J, Ungboriboonpisal S, Sriphong L (2006) A stability-indicating HPLC method for medroxyprogesterone acetate in bulk drug and injection formulation. J Pharm Biomed Anal 40:1068–1072.

    Article  CAS  PubMed  Google Scholar 

  44. Sprangler M, Mularz E (2001) A validated, stability-indicating method for the assay of dexamethasone in drug substance and drug product analyses, and the assay of preservatives in drug product. Chromatographia 54:329–334.

    Article  Google Scholar 

  45. Skrdla PJ, Abrahim A, Wu Y (2006) An HPLC chromatographic reactor approach for investigating the hydrolytic stability of a pharmaceutical compound. J Pharm Biomed Anal 41:883–890.

    Article  CAS  PubMed  Google Scholar 

  46. Bell F, Dolan JW (2006) On-column sample degradation. LC-GC N Am 24:1184–1190.

    Google Scholar 

  47. Lange J, Below E, Thede R (2004) Separate determination of mobile-phase rate constants for reversible reactions. J Liq Chrom Relat Tech 27:715–725.

    Article  CAS  Google Scholar 

  48. Zhang J, Miller RB, Jacobus R (1997) Development and validation of a stability-indicating HPLC method for the determination of degradation products in dipyridamole injection. Chromatographia 44:247–252.

    Article  CAS  Google Scholar 

  49. DiNunzio JE (1992) Pharmaceutical applications of high-performance liquid chromatography interfaced with fourier transform infrared spectroscopy. J Chromatogr 626:97–107.

    Article  CAS  Google Scholar 

  50. Chen W, Zhou P, Wong-Moon KC, Cauchon NS (2007) Identification of volatile degradants in formulations containing sesame oil using SPME/GC/MS. J Pharm Biomed Anal 44:450–455.

    Article  CAS  PubMed  Google Scholar 

  51. Kazakevich Y, LoBrutto R (2007) HPLC for pharmaceutical scientists. Wiley-Interscience, New York.

    Book  Google Scholar 

  52. Lukulay P, Hokanson G (2005) A perspective on reconciling mass balance in forced degradation studies. Pharm Tech 29:106–113.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bristol-Myers Squibb Analytical Research and Development, Provinceline Rd and Route 206, Princeton, NJ, 08540

    Anne-Françoise Aubry, Peter Tattersall & Joan Ruan

Authors
  1. Anne-Françoise Aubry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Tattersall
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joan Ruan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne-Françoise Aubry .

Editor information

Editors and Affiliations

  1. Pharmalytik, Newark, Delaware, USA

    Kim Huynh-Ba

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Aubry, AF., Tattersall, P., Ruan, J. (2009). Development of Stability Indicating Methods. In: Huynh-Ba, K. (eds) Handbook of Stability Testing in Pharmaceutical Development. Springer, New York, NY. https://doi.org/10.1007/978-0-387-85627-8_7

Download citation

Publish with us

Policies and ethics

Search

Navigation