View Article

Abstract

The detection and characterization of impurities in pharmaceuticals are pivotal aspects of ensuring the safety, efficacy, and quality of drug products. This review provides a comprehensive overview of the analytical techniques employed in the identification and quantification of impurities at various stages of pharmaceutical development, manufacturing, and quality control. Chromatographic methods, including High-Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC), are foundational for their ability to separate complex mixtures. Mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy offer high sensitivity and structural insights crucial for impurity characterization. The integration of these techniques, such as in Liquid Chromatography-Mass Spectrometry (LC-MS) and Liquid Chromatography-Nuclear Magnetic Resonance (LC-NMR), provides a synergistic approach to impurity analysis. Advanced hyphenated techniques enhance specificity and accuracy, allowing for real-time monitoring and dynamic adjustments during analysis. Challenges in chiral separation, degradation product analysis, and method validation are addressed through the sophistication of these methodologies. The review underscores the significance of data analysis and validation processes, ensuring the reliability of results in compliance with stringent regulatory standards. Overall, the continuous evolution and integration of analytical techniques play a pivotal role in shaping the future of pharmaceutical research, development, and quality assurance, emphasizing the commitment to producing pharmaceuticals of the highest quality and safety standards.

Keywords

Impurities, Hyphenated Techniques, Active Pharmaceutical Ingredients, Chromatography, Analytical Technique, Detection

Reference

  1. U.S. Food and Drug Administration. Guidance for Industry, Q3A Impurities in New Drug Substances. February 2003.
  2. U.S. Food and Drug Administration. Guidance for Industry, Q3B Impurities in New Drug Products. July 2006.
  3. Pallavi Palkhe Shilpa Kawade, International journal of chemical studies, review on hyphenated techniques, department of vhemisTrysinhgad College of pharmacy vadgaonpune
  4. Hyphenated NMR techniques Julie R. KESTING, Kenneth T. JOHANSzN and Jerzy W. JAROSZEWSKI Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Denmark.
  5. Masoom Raza Siddiqui , Zeid A. AlOthman , Nafisur Rahman Arabian journal of chemistry, Analytical techniques in pharmaceutical analysis Department of Chemistry, Aligarh Muslim University, Aligarh (UP) 202002, India
  6. Wilson ID, Brinkman UA. Hyphenation and hyper nation: The Practice and Prospects of Multiple Hyphenation. J Chromatogr A, 2003; 1000: 325-56.
  7. . Szpunar J, Lobinski R, Prange A. Hyphenated Techniques for Elemental speciation in Biological Systems. Applspect, 2003; 57(3): 102A-12A.
  8. Joshi RR, Gupta KR, Patil SS. Hyphenated Technique- A Boon To Analytical World. IJPSR, 2012; 3(11): 4184-91
  9. Ahuja S. Impurities Evaluation of Pharmaceuticals, Marcel Dekker, Inc. New York, 2006.
  10. 15. Guntupalli S, Ray UK, Murali N, Gupta PB, Kumar VJ, Satheesh D, et al. Identification, isolation and characterization of process related impurities in ezetimibe. J Pharm Biomed Anal 2014;88:385-90.
  11. Prakash L, Malipeddi H, Subbaiah BV, Lakka NS. Impurity profiling and stability-indicating UPLC method development and validation for the estimation of related impurities of halobetasol propionate in halobetasol propionate 0.05 % (w/w) cream. J Chromatogr Sci 2015;53(1):112-21.
  12. Lajin B, Steiner O, Fasshold L, Zangger K, Goessler W. The identification and chromatographic separation of a new highly analogous impurity of the active pharmaceutical ingredient icatibant. Eur J Pharm Sci 2019;132:121-124.
  13. Kumar V, Bhurta D, Sharma A, Kumar P, Bharate SB, Vishwakarma RA, et al. Impurity profiling of anticancer preclinical candidate, IIIM-290. J Pharm Biomed Anal 2019;166:1-5.
  14. Prakash L, Himaja M, Subbaiah BV, Vasudev R, Srinivasulu C, Haribabu R. Isolation, identification and characterization of degradant impurities in Tolterodine tartrate formulation. J Pharm Biomed Anal 2014;90:215-221.
  15. Zhuang T, Zhang W, Cao L, He K, Wang Y, Li J, et al. Isolation, identification and characterization of two novel process-related impurities in olanzapine. J Pharm Biomed Anal 2018;152:188- 96.
  16. Kumar N, Devineni SR, Gajjala PR, Dubey SK, Kumar P. Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR. J Pharm Anal 2017;7(6):394- 400.
  17. Karthikeyan K, Arularasu GT, Murali V, Pillai KC. Identification, isolation, characterization and response factor determination of process-related impurity in meprobamate drug substance. J Pharm Biomed Anal 2011;54(1):208-212.
  18. Reddy RB, More KR, Gupta L, Jha MS, Magar L. Identification, synthesis, isolation and characterization of new impurity in metoprolol tartrate tablets. J Pharm Biomed Anal 2016;117:104-8
  19. Darcsi A, Tóth G, Kökösi J, Béni S. Structure elucidation of a process-related impurity of dapoxetine. J Pharm Biomed Anal 2014;96:272-277.
  20. Reddy GV, Reddy BV, Haque SW, Gautam HD, Kumar P, Kumar AP, et al. Development and validation of a stabilityindicating UPLC method for rosuvastatin and its related impurities in pharmaceutical dosage forms. Quimica Nova 2011;34(2):250-5.
  21. Reddy GR, Kumar AP, Ram Reddy BV, Sreeramulu J. Application of ion-trap mass spectrometry for identification and structural determination of an unknown impurity in simvastatin. Pharmazie 2009;64(10):638-41.
  22. Ram Reddy GV, Kumar AP, Venkateswara Reddy B, Sreeramulu J, Park JH. Separation, identification and structural elucidation of a new impurity in the drug substance of amlodipine maleate using LC-MS/MS, NMR and IR. Croat Chem Acta 2010;83(4):443-9.
  23. Venkateswara Reddy B, Kumar AP, Ram Reddy GV, Sahai M, Sreeramulu J, Park JH. Stability indicating reversedphase high performance liquid chromatography method for determination of impurities in ofloxacin tablet formulations. Anal Lett 2010;43(17):2653-62.
  24. Sutar N, Garai R, Sharma US, Sharma UK. Anthelmintic activity of Platycladusorientalis leaves extract. Int. J. Parasitol. Res., 2010; 2(2): 1-3.
  25. Parimoo P, et al, A Text Book of Pharmaceutical Analysis, CBS Publishers, New Delhi: 1998; 14.
  26. Conte E, Milani R, Morali G, Abballe F. Comparison between accelerated solvent extraction and traditional extraction methods for the analysis of the herbicide diflufenican in soil. J Chromatogr A 1997;765(1):121-5.
  27. Szepesi, G., Nyiredy, S., 1996. Pharmaceutical and drugs. In: Sherma, J., Fried, B. (Eds.), Handbook of Thin-Layer Chromatography, 2nd ed. Marcel Dekker, New York, pp. 208–235.
  28. Cimpoiu, C., Hosu, A., Hodison, S., 2006. J. Pharm. Biomed. Anal. 41, 633–637.
  29. Gumieniczek, A., Hopkala, H., Bereka, A., 2004. J. Liq. Chromatogr. Relat. Technol. 27, 2057–2070.
  30. Bebawy, L.I., Moustafa, A.A., Abo-Talib, N.F., 2002. J. Pharm. Biomed Anal. 27, 779–793.
  31. Ashour, A., Hegazy, M.A.M., Moustafa, A.A., Kelani, K.O., Abdel Fattah, L.E., 2009. Drug Test. Anal. 1, 327–338.
  32. White, D., Varlashkin, P., Rusch, D.N., 1992. J. Pharm. Sci. 81, 1204–1209.
  33. Agbaba, D., Radovic, A., Vladimirov, S., Zivanov-Stakic, D., 1996. J. Chromatogr. Sci. 34, 460–464.
  34. Watson, D.G., 1999. Pharmaceutical Analysis. Churchill Livingstone, Edinburg, p. 208.
  35. Lima, E.M., Almeida Diniz, D.G., Antoniosi-Filho, N.R., 2005. J. Pharm. Biomed. Anal. 38, 678–685
  36. Zuo, Y., Zhang, L., Wu, J., Fritz, J.W., Medeiros, S., Rego, C., 2004. Anal. Chim. Acta 526, 35–39.
  37. Somuramasami, J., Wei, Y.-C., Soliman, E.F., Rustum, A.M., 2011. J. Pharm. Biomed. Anal. 54, 242–247.
  38. Frost, R.P., Hussain, M.S., Raghani, A.R., 2003. J. Sep. Sci. 26, 1097-1011.
  39. Hiriyanna, S.G., Basavaiah, K., 2008. J. Brazil Chem. Soc. 19, 397– 404.
  40. Reddy, B.P., Reddy, M.S., 2009. Int. Pharm. Tech. Res. 1, 230–234.
  41. Hashimoto, K., Urakami, K., Fujiwara, Y., Terada, S., Watanabe, C., 2001. Anal. Sci. 17, 645–648
  42. Saraji, M., Khayamian, T., Siahpoosh, Z.H., Farajmand, B., 2012. Anal. Methods 2012 (4), 1552–1559.
  43. Deconinck, E., Canfyn, M., Sacre´, P.-Y., Baudewyns, S., Courselle, P., De Beer, J.O., 2012. J. Pharm. Biomed. Anal. 70, 64–70.
  44. Look DC, Jones RL, Cantwell G. Characterization of homoepitaxial p­type ZnO grown by molecular beam epitaxy. Appl Phys Lett. 2002?81:1830.
  45. Rao RN, Nagaraju V.An overview of the recent trends in development of HPLC methods for determination of impurities in drugs. J Pharm Biomed Anal 2003;33(3):335-77.
  46. Vassort A, Barrett DA, Shaw PN, Ferguson PD, Szucs R. A generic approach to the impurity profiling of drugs using standardized and independent capillary zone electrophoresis methods coupled to electrospray ionization mass spectrometry. Electrophoresis 2005;26(9):1712-23.
  47. Mallampati S, Pauwels J, Hoogmartens J, Van Schepdael A. 12 CE in impurity profiling of drugs. Sep Sci Technol 2008;9(07):259-315.
  48. Buckau G, Duschner H, Psarros N. Characterization of humic and fulvic acids from Gorleben groundwater.Fresenius J Anal Chem. 1990?338:245–52.
  49. Rajawat J, Jhingan G. Mass spectroscopy. InData Processing Handbook for Complex Biological Data Sources 2019:1-20.
  50. Wennig R. Potential problems with the interpretation of hair  analysis results. Forensic Sci Int 2000;107(1-3):5-12.
  51. Ronowicz J, Kupcewicz B, Myd?owska J, Budzisz E. Impurity profile analysis of drug products containing acetylsalicylic acid: A chemometric approach. Cent Eur J Chem 2013;11(7):1091-1100.
  52. Herderich M, Richling E, Roscher R, Schneider C, Schwab W, Humpf HU. Application  of Atmospheric Pressure Ionisation HPLC-MS-MS for the Analysis of Natural Products. Chromatographia, 1997; 45: 127-32.
  53. Patel KN, Patel JK, Patel MP, Rajput GC, Patel HA. Introduction to Hyphenated Techniques and Their Applications In Pharmacy, Pharm. Methods, 2010; 1(1): 2-13.
  54. Joachim E. The Use of Hyphenated LC–MS Technique for Characterization of Impurity Profiles During Drug Development. J Pharm Biomed Anal, 1998; 18: 707-14.
  55. Jong D, áde Jong GJ, TháBrinkman UA. Investigation of on-line reversed-phase liquid chromatography–gas chromatography mass spectrometry as a tool for the identification of impurities  in drug substances. Analyst 1996;121(1):61-6.
  56. Patel KN, Patel JK, Patel MP, Rajput GC, Patel HA. Introduction to Hyphenated Techniques and Their Applications In Pharmacy. Pharm Method, 2010, 1(1): 1-13.
  57. John CL. Directly Coupled HPLC-NMR and HPLC-NMR-MS in Pharmaceutical Research and Development. J Chromatogr B, 2000; 748: 233-58.
  58. Albert K. On-line LC-NMR and Related Techniques. London: Wiley, 2002.
  59. John CL. Directly Coupled HPLC-NMR and HPLC-NMR-MS in Pharmaceutical Research and Development. J Chromatogr B, 2000; 748: 233-58.
  60. John KR and Richard JS, Use of Liquid Chromatography-Nuclear Magnetic Resonance Spectroscopy for the Identification of Impurities in Drug Substances, J.Chromatogr. A, 1994; 677: 385-89.
  61. Ahuja S, Scypinski S, Handbook of Modern Pharmaceutical Analysis. 1st ed., vol 3, USA; Academic Press, 2001; 149-152.
  62. Norwood DL, Mullis JO, Feinberg TN. 7 Hyphenated techniques. Sep Sci Technol 2007;8:189-235.
  63. Wolfender JL, Rodriguez S, Hostettmann K. Liquid chromatography coupled to mass spectrometry and nuclear magnetic resonance spectroscopy for the screening of plant constituents. J Chromatogr A 1998;794(1-2):299-316.
  64. Stutz H. Advances in the analysis of proteins and peptides by capillary electrophoresis with matrix?assisted laser desorption/ ionization and electrospray?mass spectrometry detection. Electrophoresis 2005;26(7?8):1254-90.
  65. Visky D, Jimidar I, Van Ael W, Vennekens T, Redlich D, De Smet M. Capillary electrophoresis?mass spectrometry in impurity profiling of pharmaceutical products. Electrophoresis 2005;26(7?8):1541-9.
  66. Van Wijk AM, Muijselaar PG, Stegman K, De Jong GJ. Capillary electrophoresis-mass spectrometry for impurity profiling of basic pharmaceuticals using non-volatile  background electrolytes. J Chromatogr A 2007;1159(1-2):175-84.
  67. Scheffel U, Rhodes BA, Natarajan TK, Wagner HN. Albumin microspheres for study of the reticuloendothelial system. J Nucl Med 1972;13(7):498-503.
  68. Guntupalli S, Ray UK, Murali N, Gupta PB, Kumar VJ, Satheesh D, et al. Identification, isolation and characterization of process related impurities in ezetimibe. J Pharm Biomed Anal 2014;88:385-90.
  69. Prakash L, Malipeddi H, Subbaiah BV, Lakka NS. Impurity profiling and stability-indicating UPLC method development and validation for the estimation of related impurities of halobetasol propionate in halobetasol propionate 0.05 % (w/w)  cream. J Chromatogr Sci 2015;53(1):112-21.
  70. Lajin B, Steiner O, Fasshold L, Zangger K, Goessler W. The identification and chromatographic separation of a new highly analogous impurity of the active pharmaceutical ingredient  icatibant. Eur J Pharm Sci 2019;132:121-124.
  71. Kumar V, Bhurta D, Sharma A, Kumar P, Bharate SB, Vishwakarma RA, et al. Impurity profiling of anticancer preclinical candidate, IIIM-290. J Pharm Biomed Anal 2019;166:1-5.
  72. Prakash L, Himaja M, Subbaiah BV, Vasudev R, Srinivasulu C, Haribabu R. Isolation, identification and characterization of degradant impurities in Tolterodine tartrate formulation. J Pharm Biomed Anal 2014;90:215-221.
  73. Zhuang T, Zhang W, Cao L, He K, Wang Y, Li J, et al. Isolation, identification and characterization of two novel process-related impurities in olanzapine. J Pharm Biomed Anal 2018;152:188-96.
  74. Kumar N, Devineni SR, Gajjala PR, Dubey SK, Kumar P. Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR. J Pharm Anal 2017;7(6):394-400.
  75. Karthikeyan K, Arularasu GT, Murali V, Pillai KC. Identification, isolation, characterization and response factor determination of process-related impurity in meprobamate drug substance. J Pharm Biomed Anal 2011;54(1):208-212.
  76. Reddy RB, More KR, Gupta L, Jha MS, Magar L. Identification, synthesis, isolation and characterization of new impurity in metoprolol tartrate tablets. J Pharm Biomed Anal 2016;117:104-8.

Photo
Sagar R. Pagade
Corresponding author

Department of Pharmaceutics , Ashokrao Mane Institute of Pharmacy, Ambap-416112, India

Photo
Sahil Agrawal
Co-author

Department of Pharmaceutics , Ashokrao Mane Institute of Pharmacy, Ambap-416112, India

Photo
Prathmesh Shejal
Co-author

Department of Pharmaceutics , Ashokrao Mane Institute of Pharmacy, Ambap-416112, India

Photo
Pranjal Chougule
Co-author

Department of Pharmaceutics , Ashokrao Mane Institute of Pharmacy, Ambap-416112, India

Photo
Nilesh Chougule
Co-author

Department of Pharmaceutics , Ashokrao Mane Institute of Pharmacy, Ambap-416112, India

Sagar Pagade*, Sahil Agrawal, Prathmesh Shejal, Pranjal Chougule, Nilesh Chougule, Detection Of Impurities: A Review On Advance In Impurities Detection And Characterization In Pharmaceuticals By Analytical Techniques, Int. J. in Pharm. Sci., 2023, Vol 1, Issue 12, 860-879. https://doi.org/10.5281/zenodo.10433875

More related articles
Impact Of Frequent Steroid Prescription To Patient...
Tejas R. Pawar, Komal A. Bankar , Vikas S. Shinde , ...
Assessment Of Proton Pump Inhibitor (PPI) Prescrip...
Darshak D Poojary, Satish S, A R Shabaraya, ...
Formulation Development & Evaluation Of Herbal Cre...
Abhishek Rajendra Putale , Rane Prashant Mangalsingh , Pinjari Am...
View more
Review Artical On Pharmacovigilance...
Aher Shailendra , Gajre Tushar , Bharitkar Rushikesh , Pagar Pratik , Mahankale Pratik , ...
Revolutionizing Herbal Therapeutics: Exploring Advanced Nanotechnology Drug Deli...
Ankita. S. Kshirsagar, Tushar Rode, Ishwari. R. Chaudhari, Anil. V. Chandewar, ...
Formulation and Evaluation of Antifungal and Muscle Relaxant Herbal Bath Bomb Co...
Chetan S. Darne, Monika P. Maske, Pawan A. Gore, Jagdish R. Baheti, ...
View more
Download PDF
Related Articles
Advancements In Pharmacotherapy for Myocardial Infarction: A Comprehensive Revie...
Aravind babu c, Satish S., ...
A Review On Novel Excipients...
Vaibhav B. Gunjal, Darshan S. Sonawane, Samruddhi K. Ahire, Pranav K. Jadhav, Yashashri K. Deore, Sh...
Exploring The Multifaceted Mechanisms Of Amphetamines And Their Impact On Neurot...
Arnab Roy, Mahesh Kumar Yadav, Abrarul Haque, Pratik Mondal, Gautam Mahto, Balraj Kumar, Nisha Kumar...
Film Forming Gels: A Review ...
Pradnya K Gangurde, Kajal A Choursiya, Saba Shaikh, Shardha Kandalkar, Khanderao Jadhav, Rishikesh B...
Impact Of Frequent Steroid Prescription To Patient For Long Term...
Tejas R. Pawar, Komal A. Bankar , Vikas S. Shinde , ...
More related articles
Impact Of Frequent Steroid Prescription To Patient For Long Term...
Tejas R. Pawar, Komal A. Bankar , Vikas S. Shinde , ...
Assessment Of Proton Pump Inhibitor (PPI) Prescription Patterns In A Tertiary Ca...
Darshak D Poojary, Satish S, A R Shabaraya, ...
Formulation Development & Evaluation Of Herbal Cream For Wound Healing Activity...
Abhishek Rajendra Putale , Rane Prashant Mangalsingh , Pinjari Aman Siraj , Sneha Abhishek Vikhe, Ro...
View more
Impact Of Frequent Steroid Prescription To Patient For Long Term...
Tejas R. Pawar, Komal A. Bankar , Vikas S. Shinde , ...
Assessment Of Proton Pump Inhibitor (PPI) Prescription Patterns In A Tertiary Ca...
Darshak D Poojary, Satish S, A R Shabaraya, ...
Formulation Development & Evaluation Of Herbal Cream For Wound Healing Activity...
Abhishek Rajendra Putale , Rane Prashant Mangalsingh , Pinjari Aman Siraj , Sneha Abhishek Vikhe, Ro...
View more

Copyright © 2023 IJPS. All rights reserved