Author(s):
Gayatri S. Patil, Amol R. Pawar, Pankaj S. Patil, Vikas V. Patil, Kalpesh S. Wagh
Email(s):
gayatripatil4253@gmail.com
DOI:
10.52711/0974-4150.2026.00071 
Address:
Gayatri S. Patil1*, Amol R. Pawar1,3, Pankaj S. Patil1, Vikas V. Patil1, Kalpesh S. Wagh2
1Department of Quality Assurance, Kisan Vidya Prasarak Sanstha's Institute of Pharmaceutical Education, Boradi 425428, India.
2Department of Pharmaceutics, Kisan Vidya Prasarak Sanstha's Institute of Pharmaceutical Education, Boradi 425428, India.
3Research Scholar, Sankalchand Patel University, Visnagar 384315, Gujarat, India.
*Corresponding Author
Published In:
Volume - 19,
Issue - 5,
Year - 2026
ABSTRACT:
Impurity profiling is fundamental to pharmaceutical quality assurance, underpinning the safety, efficacy, and regulatory acceptability of drug substances and finished products. A landmark workshop convened by the American Association of Pharmaceutical Scientists (AAPS) highlighted the need for coordinated scientific and regulatory strategies to identify, monitor, and control impurities throughout drug development. Pharmaceutical impurities—including organic degradation products, inorganic residues, residual solvents, synthetic by-products, genotoxic impurities, and excipient–API interaction products—can compromise drug stability and patient safety if inadequately controlled. Internationally harmonized frameworks such as ICH Q3A/Q3B, ICH Q3C, and ICH M7 provide threshold-based approaches to impurity identification, qualification, and toxicological assessment. Concurrent advances in analytical technology—HPLC, UPLC, LC-MS, GC-MS, ICP-MS, and NMR—have substantially improved trace-level impurity detection, while the integration of Process Analytical Technology (PAT) enables real-time monitoring within a quality-by-design (QbD) framework. Growing attention to extractables and leachables, continuous manufacturing, and predictive toxicology further reflects the increasing complexity of impurity management. This review synthesizes current impurity classification schemes, regulatory expectations, analytical methodologies, and emerging trends, and argues for a unified, multidisciplinary approach to impurity profiling in contemporary pharmaceutical development.
Cite this article:
Gayatri S. Patil, Amol R. Pawar, Pankaj S. Patil, Vikas V. Patil, Kalpesh S. Wagh. Impurity Profiling in Active Pharmaceutical Ingredients and Finished Products: Trends, Tools, and Quality Risk Management Approaches. Asian Journal of Research in Chemistry. 2026; 19(5):491-5. doi: 10.52711/0974-4150.2026.00071
Cite(Electronic):
Gayatri S. Patil, Amol R. Pawar, Pankaj S. Patil, Vikas V. Patil, Kalpesh S. Wagh. Impurity Profiling in Active Pharmaceutical Ingredients and Finished Products: Trends, Tools, and Quality Risk Management Approaches. Asian Journal of Research in Chemistry. 2026; 19(5):491-5. doi: 10.52711/0974-4150.2026.00071 Available on: https://www.ajrconline.org/AbstractView.aspx?PID=2026-19-5-12
REFERENCES:
1. Rahman ML. Strategic impurity control in next-generation pharmaceuticals: analytical technologies, toxicological assessment, and regulatory integration.
2. Nagpal S, Upadhyay A, Bhardwaj TR, Thakkar A. A review on need and importance of impurity profiling. Current Pharmaceutical Analysis. 2011; 7(1): 62-70.
3. Görög S. Identification and determination of impurities in drugs. 1st ed. Budapest: Elsevier; 2000. Vol. 4, p. 772.
4. Misra B, Thakur A, Mahata PP. Pharmaceutical impurities: a review.
5. Kushwaha P. The organic impurities in pharmaceuticals. Pharmainfo. 2008; 6(4).
6. Ahuja S. Isolation and characterization of pharmaceutical impurities evaluation. New York: Marcel Dekker; 2000.
7. Damle MC, et al. Development and validation of stability indicating HPTLC method for determination of ofloxacin and ketorolac tromethamine in combination. J Adv Sci Res 2011; 2(3): 77-82.
8. Connor KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals – a handbook for pharmacists. New York: John Wiley & Sons; 1986.
9. ICH Harmonised Tripartite Guideline. Impurities: guideline for residual solvents (Q3C-R8). Available online: https://database.ich.org/sites/default/files/ICH_Q3C-R8_Guideline_Step4_2021_0422_1.pdf (accessed 15 December 2024).
10. Strickley RG. Solubilizing excipients in oral and injectable formulations. In: Pharmaceutical Research. Springer; 2004.
11. The United States Pharmacopeia. Chapter <467> Residual solvents. Available online: https://doi.usp.org/USPNF/USPNF_M99226_08_01.html (accessed 15 December 2024).
12. Welton T. Solvents and sustainable chemistry. Proc R Soc A. 2015; 471(2183): 20150502. doi:10.1098/rspa.2015.0502.
13. Guidance for Industry Q3B(R2). Impurities in new drug products.
14. Wirth DD, et al. Maillard reaction of lactose and fluoxetine hydrochloride, a secondary amine. J Pharm Sci. 1998; 87: 31-39.
15. Goodhart FW. Lactose. In: Wade A, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 2nd ed. London: Pharmaceutical Press; 1994. p. 258-259.
16. Senderoff RI, Mahjour M, Radebaugh GW. Characterization of adsorption behaviour by solid dosage form excipients in formulation development. Int J Pharm. 1992; 83: 65-72.
17. Czaja J, Mielck JB. Solid-state degradation kinetics of nitrazepam in the presence of colloidal silica. Pharm Acta Helv. 1982; 57(5-6): 133-155.
18. Deepti J, Pawan Kumar B. J Pharm Biomed Anal. 2013; 86: 11-35.
19. Teasdale A, Fenner S, Ray A, Ford A, Philips A. Org Process Res Dev. 2010; 14: 943-945.
20. Snodin DJ. Org Process Res Dev. 2010; 14: 960-976.
21. ICH Harmonised Tripartite Guideline Q3A(R2). Impurities in New Drug Substances. 2006.
22. ICH Q6A. Specifications: test procedures and acceptance criteria for new drug substances and drug products: chemical substances. International Conference on Harmonisation; 1999.
23. ICH Q3B(R2). Impurities in New Drug Products. 2006.
24. Residual Detergent Contaminations (ICH Q3C).
25. ICH Q3C(R6). Impurities: Guidelines for Residual Solvents. 2006.
26. ICH Q9. Quality Risk Management. 2005.
27. ICH M7. Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk. Guidance for Industry; 2014.
28. Indian Pharmacopoeia. Indian Pharmacopoeia Commission, Ghaziabad, Ministry of Health and Family Welfare, Government of India; 2018. Int J Pharm Sci Rev Res. 2015; 5(07): 232-239. Available: http://dx.doi.org/10.7439/ijpc.
29. Council of Europe. European Pharmacopoeia: background and mission. 2020. Available: https://www.edqm.eu/en/European-Pharmacopoeia.
30. Council of Europe. Available: https://www.edqm.eu/sites/default/files/01_schedule_2019_portrait.pdf.
31. United States Pharmacopeia. Available: https://qualitymatters.usp.org/what-us-pharmacopeia.
32. Kumara ST, Kamarthi SV, Bukkapatnam S, Lee J. Sensor based monitoring for real-time quality control in manufacturing.
33. Liliana L. A new model of Ishikawa diagram for quality assessment. University "Constantin Brâncuşi" of Targu-Jiu, Romania.
34. Read EK, Park JT, Shah RB, Riley BS, Brorson KA, Rathore AS. Biotechnol Bioeng. 2009; 105(2): 276-284.
35. Read EK, Park JT, Shah RB, Riley BS, Brorson KA, Rathore AS. Biotechnol Bioeng. 2009; 105(2): 285-295.
36. Freund H, Sundmacher K. Chem Eng Process 2008; 47: 2051-2060.
37. Koch MV. Anal Bioanal Chem 2006; 384: 1049-1053.
38. Simon H. Process applications of analytical instruments. Instrum Autom. 1956; 29: 1141-1145.
39. Clevett KJ. Process analyzer technology. New York: Wiley-Interscience; 1986.
40. Koch KH. Process Analytical Chemistry. New York: Springer; 1997.
41. Chalmers JM, ed. Spectroscopy in Process Analysis. Boca Raton, FL: CRC Press; 2000.
42. Bakeev KA, ed. Process analytical technology: spectroscopic tools and implementation strategies for the chemical and pharmaceutical industries. Oxford: Blackwell Publishing. 2005.
43. Beebe KR, Blaser WW, Bredeweg RA, Chauvel JP, Harner RS, Lapack M, Leugers A, Martin DP, Wright LG, Yalvac ED. Anal Chem. 1993; 65(12): R199-R216.
44. Workman J, Koch M, Veltkamp DJ. Anal Chem. 2003; 75: 2859-2876.
45. De Fatima L, de Lira B, Vasconcelos FVC, Pereira CF, Paim APS, Stragevitch L, Pimentel MF. Fuel. 2010; 89: 405-409.
46. Prinsloo NM, Engelbrecht JP, Mashapa TN, Strauss MJ. Appl Catal A-Gen. 2008; 344: 20-29.
47. Halstensen M, Bakker P, Esbensen KH. Chemometr Intell Lab. 2006; 84: 88-97.
48. Seasholtz MB. Chemometr Intell Lab. 1999; 45: 53-63.
49. Fernandes HL, Raimundo IM, Pasquini C, Rohwedder JJR. Talanta. 2008; 75: 804-810.
50. Qu H, Alatalo H, Hatakka H, Kohonen J, Louhi-Kulanen M. J Cryst Growth. 2009; 311: 3466-3475.
51. Ward HW, Sistare FE. Anal Chim Acta 2007; 595: 319-322.
52. Liu KT, Chen CH. Determination of impurities in pharmaceuticals: why and how? Submitted 25 September 2018; reviewed 3 January 2019; published 31 January 2019. doi:10.5772/intechopen.83849.
53. Rao RN, Vali RM, Ramachandra B, Raju SSN. J Pharm Biomed Anal. 2011; 54: 279.
54. Nguyen DT, Guillarme D, Rudaz S, Veuthey JL. J Sep Sci. 2006; 29(12): 1836.
55. Swartz ME. J Liq Chromatogr Related Technol. 2005; 28: 1253.
56. Reddy YR, Nandan SR, Bharathi DV, Nagaraju B, Reddy SS, et al. LC and LC-MS/MS study of forced decomposition behavior of anastrozole and establishment of validated stability-indicating analytical method for impurities estimation in low dose anastrozole tablets. J Pharm Biomed Anal. 2009; 50(3): 397-404.
57. Akshatha HS, Gurupadayya BM. Application of liquid chromatography coupled with mass spectrometry in the impurity profiling of drug substances and products. Asian J Pharm Clin Res. 2018; 11: 30-37.
58. Patil PP, Kasture VS, Prakash KV. Impurity Profiling: Emerging Trends in Quality Control of Pharmaceuticals.
59. ICH Harmonised Tripartite Guideline. Quality risk management (Q9). Current Step 4 version, 9 November 2005.
60. International Council for Harmonisation. ICH Q3A(R2): impurities in new drug substances. 2022.
61. Skoog DA, Holler FJ, Crouch SR. Principles of Instrumental Analysis. 7th ed. Cengage; 2018.