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Abstract

Purity profiling involves the meticulous gathering and analysis of information to ascertain the biological safety of specific impurities, underscoring its crucial role and extensive scope within pharmaceutical research. In the realm of pharmaceuticals, the term "impurity" lacks a precise definition. Impurity profiling encompasses the identification, structural clarification, and quantitative assessment of impurities and degradation products present in bulk medicinal materials and pharmaceutical formulations. Given that undisclosed and potentially harmful impurities pose a threat to health, their detection and quantification through meticulous methods are imperative to bolster the safety of drug therapy, rendering impurity profiling increasingly pivotal in modern pharmaceutical analysis. Impurities are commonly denoted by terms such as residual solvents, byproducts, transformation products, degradation products, interaction products, and related substances. Determining impurity identities involves employing diverse chromatographic techniques alongside compliance with CGMP (Current Good Manufacturing Practices), QC (Quality Control), QA (Quality Assurance), and water activity examinations. Furthermore, a pharmaceutical ingredient must meet the criteria for novel impurities. The process of segregating and characterizing impurities assumes great significance as it enables the accumulation and assessment of data that establishes biological safety, thus highlighting the indispensability and potential of drug impurity profiling in pharmaceutical research. To effectively segregate and quantify impurities, an array of instrumental analytical methods has been consistently employed The detection and regulatory assessment of organic impurities present a formidable challenge due to the myriad sources of such impurities, including microbiological contamination, API (Active Pharmaceutical Ingredient) breakdown products, and trace amounts of intermediates

Keywords

Pharmaceutical impurities, Impurity, Pharmacopeia, Companies, Manufacturing, Method, Synthesis, etc

Reference

  1. Barber HJ. Historical Aspects of Chemotherapy: Six Essays. May and Baker; 1978.
  2. Ahuja S, Alsante KM, editors. Handbook of isolation and characterization of impurities in pharmaceuticals. Academic press; 2003.
  3. Roy J. Pharmaceutical impurities—a mini-review. AAPs PharmSciTech. 2002 Jun;3(2):1-8.
  4. Ahuja S, Alsante KM, editors. Handbook of isolation and characterization of impurities in pharmaceuticals. Academic press; 2003.
  5. S. Ahuja. Impurities Evaluation of Pharmaceuticals, Marcel Dekker, Inc. New York, 2006.
  6. Ahuja S, Scypinski S, editors. Handbook of modern pharmaceutical analysis. Academic press; 2001 Aug 9.
  7. Roy J. Pharmaceutical impurities—a mini-review. AAPs PharmSciTech. 2002 Jun;3(2):1-8.
  8. Keitel S. Impurity Profiles in Active Pharmaceutical Ingredients. In EU/Swiss medic GMP Workshop Beijing University 2006 Sep (Vol. 9).
  9. Alsante KM, Boutros P, Couturier MA, Friedmann RC, Harwood JW, Horan GJ, Jensen AJ, Liu Q, Lohr LL, Morris R, Raggon JW. Pharmaceutical impurity identification: a case study using a multidisciplinary approach. Journal of Pharmaceutical Sciences. 2004 Sep;93(9):2296-309.
  10. International Conference on Harmonization (2000) Draft Revised Guidance on Impurities in New Drug Substances. Federal Register Q3A(R) 65 (140): 45085.
  11. International Conference on Harmonization (2000) Draft Revised Guidance on Impurities in New Drug Products. Federal Register Q3B(R) 65 (139): 44791.
  12. International Conference on Harmonization (1997) Impurities, Q3C- Guidelines for Residual Solvents, Q3C. Federal Register 62(247): 67377.
  13. International Conference on Harmonization (1999) Specifications, Q6A: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products. Chemical substances 65 (146):67488.
  14. Görög S, Babjak M, Balogh G, Brlik J, Csehi A, Dravecz F, Gasdag M, Horvath P, Lauko A, Varga K. Drug impurity profiling strategies. Talanta. 1997 Sep 1;44(9):1517-26.
  15. Guideline IH. Impurities in new drug substances Q3A (R2). In Proceedings of the international conference on harmonization of technical requirements for registration of pharmaceuticals for human use, Geneva, Switzerland 2006 Oct 25 (Vol. 25).
  16. Deshpande MM, Bhalerao MH, Pabale PD. A Review on Impurity Profiling, Degradation Studies, and Bioanalytical Methods of Anti-diabetic Drugs.
  17. Pharmacopoeia I. Ghaziabad: Indian Pharmacopoeia Commission. Govt. of India-Ministry of Health and Family Welfare. 2014:1948.
  18. Dhangar KR, Jagtap RB, Surana SJ, Shirkhedkar AA. Impurity profiling of drugs towards safety and efficacy: theory and practice. Journal of the Chilean Chemical Society. 2017 Jun;62(2):3543-57.
  19. Beckett, A.H; Stanlake, J.B. Practical Pharmaceutical Chemistry. CBS Publishers and distributors: New Delhi, 2002.
  20. Ahuja S, Scypinski S, editors. Handbook of modern pharmaceutical analysis. Academic press; 2001 Aug 9.
  21. 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.
  22. Connors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals: a handbook for pharmacists. John Wiley & Sons; 1986 Oct 13.
  23. Nagpal S, Upadhyay A, R Bhardwaj T, Thakkar A. A review on need and importance of impurity profiling. Current Pharmaceutical Analysis. 2011 Feb 1;7(1):62-70
  24. Görög S, editor. Identification and determination of impurities in drugs. Elsevier; 2000 May 19.
  25. Condorelli G, De Guidi G, Giulfrido S. Molecular mechanisms of photosensitization induced by drugs XII. Photochemistry and photosensitization of rufloxacin: An unusual photodegradation path for the antibacterials containing a fluoroquinolone like chromophore. Photochem Photobiol 1999;70:280-6
  26. Connors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals: a handbook for pharmacists. John Wiley & Sons; 1986 Oct 13.
  27. Hoerle SL, Evans KD, Snider BG. HPLC Determination of Impurities in a 3 rd Generation Cephalosporin. InSomerset, New Jersey: Eastern Analytical Symposium 1992 Nov 16.
  28. Roy J, Bhuiyan K, Faruque A. Injectable ergometrine: Stability and packaging for developing countries. Indian Drugs1997; 34:634-6.
  29. Kumar V, Sunder N, Potdar A. Critical factors in developing pharmnaceutical formulations- An overview. Part 2. Pharm Technol 1992;16:86-8
  30. Smith A, Pennefather PM, Kaye SB. Fluoroquinolones - place in ocular therapy. Drugs 2001;61:747-61
  31. Pilaniya K, Chandrawanshi HK, Pilaniya U, Manchandani P, Jain P, Singh N. Recent trends in the impurity profile of pharmaceuticals. Journal of Advanced Pharmaceutical Technology & Research. 2010 Jul;1(3):302.
  32. Hatakka H, Alatalo H, Palosaari S. Effect of Impurities and additives on crystal Growth Available from: http://www2.lut. fi/~hhatakka/docit/impure.html.[Last accessed on 2010].
  33. Jacobs P, Dewe W, Flament A, Gibella M, Ceccato A. A new validation approach applied to the GC determination of impurities in organic solvents. Journal of pharmaceutical and biomedical analysis. 2006 Feb 13;40(2):294-304.
  34. Gimeno P, Besacier F, Bottex M, Dujourdy L, ChaudronThozet H. A study of impurities in intermediates and 3, 4 methylenedioxymethamphetamine (MDMA) samples produced via reductive amination routes. Forensic Sci Int 2005;155:141-57.
  35. Ahuja S. Impurities evaluation of pharmaceuticals. Informa Health Care; 1998 Mar 27.
  36. Pilaniya K, Chandrawanshi HK, Pilaniya U, Manchandani P, Jain P, Singh N. Recent trends in the impurity profile of pharmaceuticals. Journal of Advanced Pharmaceutical Technology & Research. 2010 Jul;1(3):302.
  37. Markovic I. Evaluation of safety and quality impact of extractable and leachable substances in therapeutic biologic protein products: A risk-based perspective. Informa 2007;6:487-91.
  38. Roy J, Islam M, Khan AH, Das SC, Akhteruzzaman M, Deb AK, Alam AH M. Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity. J Pharm Sci. 2001;(90):541-544.
  39. Roy J, Bhuiyan K, Faruque A, Sobahan M, AlFarooque M. Injectable ergometrine: stability and packaging for developing countries. Indian Drugs. 1997;34(11):634-636.
  40. Bari SB, Kadam BR, Jaiswal YS, Shirkhedkar AA. Impurity profile: Significance in Active Pharmaceutical Ingredient. Eurasian journal of analytical chemistry. 2007 Mar 1;2(1).
  41. Hoq MM, Morsheda SB, and Gomes DJ. Development of appropriate preservative system for liquid antacid: bacterial contaminants in antacid samples. Bang J Microbiology. 1991;8(1):5-9.
  42. Buhler V. Vademecum for Vitamin Formulation. Stuttgart, Germany: Wiss. Verl-Ges; 1988.
  43. Roy J, Mahmud M, Sobhan A, Aktheruzzaman M, Al-Farooque M, Ali AE. Marketed vitamin B-complex injectables: stability and mutual interaction. Drug development and industrial pharmacy. 1994 Jan 1;20(13):2157-63.
  44. Connors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals: a handbook for pharmacists. John Wiley & Sons; 1986 Oct 13.
  45. Hoerle SL, Evans KD, Snider BG. HPLC Determination of Impurities in a 3 rd Generation Cephalosporin. InSomerset, New Jersey: Eastern Analytical Symposium 1992 Nov 16.
  46. Kumar V, Sunder N, Potdar A. CRITICAL FACTORS IN DEVELOPING PHARMACEUTICAL FORMULATIONS: AN OVERVIEW. II. Pharmaceutical technology. 1992;16(4).
  47. Roy J. Pharmaceutical impurities—a mini-review. AAPs PharmSciTech. 2002 Jun;3(2):1-8.
  48. Bari SB, Kadam BR, Jaiswal YS, Shirkhedkar AA. Impurity profile: Significance in Active Pharmaceutical Ingredient. Eurasian journal of analytical chemistry. 2007 Mar 1;2(1).
  49. Bart, C. J. Separation Techniques - Additives in Polymers: indusrtrial analysis and applications. John Wiley and Sons. 2005, p. 212.
  50. Still, W. C.; Kahn, M.; Mitra, A. Rapid chromatographic technique for preparative separations with moderate resolution. J. Org. Chem., 1978, 43(14), 2923-2925.
  51. Bakshi M, Singh S. Development of validated stability-indicating assay methods—critical review. Journal of pharmaceutical and biomedical analysis. 2002 Jun 15;28(6):1011-40.
  52. Pal K, Raju MB, Kumar KP, Chakravorthy R. Simultaneous Determination of Telmisartan and Ramipril in Tablet Dosage Form by Spectrophotometry. Parameters. 2010 Sep 28;97(101.60):97-103.
  53. Borole, T.C.; Mehendre, R.; Damle, M.C.; Bothara K.G. Development and validation of stability indicating HPTLC method for determination of Prasugrel. J. Chem. Pharm. Res., 2010, 2(4), 907-913.
  54. Wankhede, S.B; Mahale, D.K; Chitlange, S.S. Stability-indicating HPTLC method for simultaneous determinationof Drotaverine and Aceclofenac in tablet formulation. Der. Pharma. Chemica, 2010, 2(5), 107-117.
  55. Makhija, S.N; Vavia, P.R. Stability indicating HPTLC method for the simultaneous determination of pseudoephedrine and cetirizine in pharmaceutical formulations. J. Pharm. Biomed. Anal., 2001, 25, 663-667.
  56. Subasranjan, A.; Suresh, P.; Srinivasulu, C.; Hemant, R. A validated stability-indicating gas chromatography method for determination of divalproex sodium impurities in pharmaceutical preparation. Drug Test. Anal., 2010, 2(4), 182-1.
  57. Hunt-Fugate, A.K; Hennessey, C.K; Kazarian, C.M. Stability of fluconazole in injectable solutions. American J Hospital Pharm., 1993, 50(6), 1186-1187.
  58. Pal K, Raju MB, Kumar KP, Chakravarthy R. Simultaneous Determination of Telmisartan and Ramipril in Tablet Dosage Form by Spectrophotometry. Parameters. 2010 Sep 28;97(101.60):97-103.
  59. Raymond S. Chromatographic detectors design: Function and operation. Chromatographic science series. 1995;73:201-4.
  60. Jadhav Ankush P, Kedar Tejashree R, Gaikwad Vishal S, Jadhav Ravindra T. RECENT APPROACHES FOR IMPURITY PROFILING: A REVIEW.
  61. Shou M, Galinada WA, Wei YC, Tang Q, Markovich RJ, Rustum AM. Development and validation of a stability-indicating HPLC method for simultaneous determination of salicylic acid, betamethasone dipropionate and their related compounds in Diplomatic Lotion®. Journal of pharmaceutical and biomedical analysis. 2009 Oct 15;50(3):356-61.
  62. Rao RN, Nagaraju V. Separation and determination of synthetic impurities of norfloxacin by reversed-phase high performance liquid chromatography. Journal of pharmaceutical and biomedical analysis. 2004 Mar 10;34(5):1049-56.
  63. Zaidi ZR, Sena FJ, Basilio CP. Stability assay of allantoin in lotions and creams by high-pressure liquid chromatography. Journal of Pharmaceutical Sciences. 1982 Sep 1;71(9):997-9.
  64. Still WC, Kahn M, Mitra A. Rapid chromatographic technique for preparative separations with moderate resolution. The Journal of Organic Chemistry. 1978 Jul;43(14):2923-5.
  65. Nagpal S, Upadhyay A, R Bhardwaj T, Thakkar A. A review on need and importance of impurity profiling. Current Pharmaceutical Analysis. 2011 Feb 1;7(1):62-70.
  66. Hamdan II, Jaber AB, Abushoffa AM. Development and validation of a stability indicating capillary electrophoresis method for the determination of metformin hydrochloride in tablets. Journal of pharmaceutical and biomedical analysis. 2010 Dec 15;53(5):1254-7.
  67. Sauber, C.; Ross, G. Impurity Profiling with Capillary Electrophoresis/Ion Trap Mass Spectrometry. Application Note, Agilent Technologies, USA
  68. Blomberg LG, Wan H. Determination of enantiomeric excess by capillary electrophoresis. ELECTROPHORESIS: An International Journal. 2000 Jun 1;21(10):1940-52.
  69. Terabe S. Capillary separation: micellar electrokinetic chromatography. Annual Review of Analytical Chemistry. 2009 Jul 19;2:99-120.
  70. da Silva Sangoi M, Magalhães da Silva L, D'Avila FB, Dalmora SL. Determination of fluticasone propionate in nasal sprays by a validated stability-indicating MEKC method. Journal of chromatographic science. 2010 Sep 1;48(8):641-6.
  71. . Bretnall AE, Hodgkinson MM, Clarke GS. Micellar electrokinetic chromatography stability indicating assay and content uniformity determination for a cholesterol-lowering drug product. Journal of pharmaceutical and biomedical analysis. 1997 May 1;15(8):1071-5.
  72. Gupta Raghav1 , Dr. Jain Suresh 1, Gupta Ankit1. a review on the impurity profile of pharmaceuticals. international journal of drug formulation and research.2014,april 15

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Aditi A Kokande
Corresponding author

Divine College of Pharmacy, Satana

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Sanket S Gite
Co-author

Divine College of Pharmacy, Satana

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Nikit S Thakare
Co-author

Divine College of Pharmacy, Satana

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Aniket B Bairagi
Co-author

Divine College of Pharmacy, Satana

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Shubham R Jadhav
Co-author

Divine College of Pharmacy, Satana

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Himmat D Sawant
Co-author

Divine College of Pharmacy, Satana

Sanket S. Gite, Nikit S. Thakare, Aditi A. Kokande, Aniket B. Bairagi, Shubham R. Jadhav, Himmat D. Sawant, Cutting-edge Techniques for Impurity Profiling in Pharmaceutical Analysis: A brief Overview, Int. J. in Pharm. Sci., 2023, Vol 1, Issue 11, 571-587. https://doi.org/10.5281/zenodo.10213447

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