Skip to content
2000
image of Identification and Detection of Pharmaceutical Impurities for Ensuring Safety Standard of Medicine: Hyphenated Analytical Techniques and Toxicity Measurements

Abstract

Impurity separation and detection are essential processes in the pharmaceutical industry to preserve the quality of drugs as the impurities have the potential to significantly impair the therapeutic efficacy of an active ingredient and have negative effects on pharmaceutical formulations. The primary determinant of drug development is the creation of products that adhere to the highest standards of quality and safety, with a particular emphasis on effectively managing impurities in the therapeutic ingredients. To ensure that the resulting pharmaceutical possesses a high level of safety, meticulous identification, precise quantification, and stringent management of any extraneous components present in the drug ingredient need to be performed. The literature was compiled from different databases, such as DOAJ, PubMed, Research Gate, Google Scholar, Scopus, and Science Direct. Several organic and inorganic contaminants that are frequently present in final products and active pharmaceutical ingredients (APIs) were covered, along with the crucial section for quality control and fundamental details on their security, toxicity, detection limits, and quantification limitations. Pharmaceutical companies resolve the problem of the presence of impurities by adhering to strict regulatory requirements set by reputable agencies, like the ICH, USFDA, EMA, and PMDA. Also, impurity profiling is required for the regulatory submissions of new drug candidates. In some pharmacopoeias, impurity profiling and reporting are also included. To identify and measure contaminants, a variety of analytical techniques are employed, as discussed in this article. This paper covers the scientific features of contaminants present in pharmaceutical preparations, their prevention strategies, and the application of state-of-the-art analytical techniques for their detection.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cds/10.2174/0115748863361289250324042233
2025-05-14
2025-09-27

  • From This Site

    /content/journals/cds/10.2174/0115748863361289250324042233
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Görög S. The importance and the challenges of impurity profiling in modern pharmaceutical analysis. Trends Analyt. Chem. 2006 25 8 755 757 10.1016/j.trac.2006.05.011
    [Google Scholar]
  2. U.S. Food and Drug Administration. Guidance for Industry, Q3B, Impurities in New Drug Products (Revision 3). Food. Drug. 2006 1 1 1 13
    [Google Scholar]
  3. U.S. Food and Drug Administration. Guidance for Industry, Q3A(R) Impurities in New Drug Substances. Food. Drug. 2008 1 1 1 10
    [Google Scholar]
  4. Pawlak Z. Clark B.J. The assay and resolution of the beta-blocker atenolol from its related impurities in a tablet pharmaceutical dosage form. J. Pharm. Biomed. Anal. 1992 10 5 329 334 10.1016/0731‑7085(92)80048‑R 1511034
    [Google Scholar]
  5. Lohr L.L. Sharp T.R. Alsante K.M. Hatajik T.D. Isolation and identification of process related impurities and degradation products from pharmaceutical drug candidates. Part II: The roles of NMR and mass spectrometry. Am. Pharm. Rev. 2001 1 1 7
    [Google Scholar]
  6. Narang A.S. Desai D. Badawy S. Impact of excipient interactions on solid dosage form stability. Excipient applications in formulation design and drug delivery Cham Springer 2015 93 137 10.1007/978‑3‑319‑20206‑8_5
    [Google Scholar]
  7. U.S. Food and drug administration. Guidance for industry, Q6A specifications: Test procedures and acceptance criteria for new drug substances and new drug products: Chemical substances. Food. Drug. 2000 1 1 1 8
    [Google Scholar]
  8. Alsante K.M. Boutros P. Couturier M.A. Friedmann R.C. Harwood J.W. Horan G.J. Jensen A.J. Liu Q. Lohr L.L. Morris R. Raggon J.W. Reid G.L. Santafianos D.P. Sharp T.R. Tucker J.L. Wilcox G.E. Pharmaceutical impurity identification: A case study using a multidisciplinary approach. J. Pharm. Sci. 2004 93 9 2296 2309 10.1002/jps.20120 15295790
    [Google Scholar]
  9. Pan C. Liu F. Ji Q. Wang W. Drinkwater D. Vivilecchia R. The use of LC/MS, GC/MS, and LC/NMR hyphenated techniques to identify a drug degradation product in pharmaceutical development. J. Pharm. Biomed. Anal. 2006 40 3 581 590 10.1016/j.jpba.2005.08.020 16242883
    [Google Scholar]
  10. Alsante K. Ando A. Brown R. Ensing J. Hatajik T. Kong W. Tsuda Y. The role of degradant profiling in active pharmaceutical ingredients and drug products. Adv. Drug Deliv. Rev. 2007 59 1 29 37 10.1016/j.addr.2006.10.006 17187892
    [Google Scholar]
  11. Abdin A.Y. Yeboah P. Jacob C. Chemical impurities: An epistemological riddle with serious side effects. Int. J. Environ. Res. Publ. Heal. 2020 17 3 1030 10.3390/ijerph17031030 32041209
    [Google Scholar]
  12. Josephs J.L. Sanders M Shipkova P Detection and characterization of pharmaceutical metabolites, degradants and impurities by the application of MS/MS software algorithms. Techn. Prog. 2007 5 7 2140 10.7439/ijpc.v5i7.2140
    [Google Scholar]
  13. Ahuja S. Handbook of Modern Pharmaceutical Analysis. Cambridge, US Academic Press 2001 298
    [Google Scholar]
  14. Roy J. Bhuiyan K. Faruque A. Sobahan M. AlFarooque M. Injectable ergometrine: Stability Saibaba et al. European Journal of Pharmaceutical and Medical research packaging for developing countries. Ind. Dru. 1997 34 11 634 636
    [Google Scholar]
  15. Patel A.B. Bundheliya A.R. Vyas A.J. Patel N.K. Patel A.I. Lumbhani A.N. A review on metal impurities in pharmaceuticals. Asi. J. Pharma. Analy. 2021 11 3 212 222 10.52711/2231‑5675.2021.00038
    [Google Scholar]
  16. Wollein U. Bauer B. Habernegg R. Schramek N. Potential metal impurities in active pharmaceutical substances and finished medicinal products – A market surveillance study. Eur. J. Pharm. Sci. 2015 77 100 105 10.1016/j.ejps.2015.05.028 26036232
    [Google Scholar]
  17. Committee for Medicinal Products for Human Use, Guideline on the Limits of Genotoxic Impurities. London, UK European Medicines Agency 2004 1 6
    [Google Scholar]
  18. Bobst S. Sukumar G. Genotoxic impurities in pharmaceutical products regulations and analysis. Agil. Technol. 2013 6 1 6
    [Google Scholar]
  19. Provera S. Martini L. Guercio G. Turco L. Costa L. Marchioro C. Application of LC-NMR and HR-NMR to the characterization of biphenyl impurities in the synthetic route development for vestipitant, a novel NK1 antagonist. J. Pharm. Biomed. Anal. 2010 53 3 389 395 10.1016/j.jpba.2010.04.027 20478677
    [Google Scholar]
  20. International conferences on harmonization, draft revised guidance on impurities in new drug substances. Q3A(R). Fed. Regist. 2000 65 140 45085 45090
    [Google Scholar]
  21. El Deeb S. Hasemann P. Wätzig H. Strategies in method development to quantify enantiomeric impurities using CE. Electrophoresis 2008 29 17 3552 3562 10.1002/elps.200800081 18803216
    [Google Scholar]
  22. Ahuja S. Impurities Evaluation of Pharmaceuticals. New York Marcel Dekker 1998 1 6
    [Google Scholar]
  23. International conference on harmonization impurities, q3c- guidelines for residual solvents, Q3C. Fed. Regist. 1997 62 247 67377
    [Google Scholar]
  24. Jacobs P. Dewé W. Flament A. Gibella M. Ceccato A. A new validation approach applied to the GC determination of impurities in organic solvents. J. Pharm. Biomed. Anal. 2006 40 2 294 304 10.1016/j.jpba.2005.06.036 16143480
    [Google Scholar]
  25. Wozniak T.J. Bopp R.J. Jensen E.C. Chiral drugs: An industrial analytical perspective. J. Pharm. Biomed. Anal. 1991 9 5 363 382 10.1016/0731‑7085(91)80160‑B 1932271
    [Google Scholar]
  26. Shah S.R. Patel M.A. Naik M.V. Pradhan P.K. Upadhyay U.M. Recent approaches of impurity profiling in pharmaceutical analysis: a review. Int. J. Pharm. Sci. Res. 2012 3 10 3603 3617
    [Google Scholar]
  27. Roy J. Pharmaceutical impurities: A mini-review. AAPS PharmSciTech 2002 3 2 1 8 10.1208/pt030206 12916943
    [Google Scholar]
  28. Sapra A. Kakkar S. Narasimhan B. Sources of impurities: A Review. Int. Res. J. Pharm. 2012 3 1 57 59
    [Google Scholar]
  29. International conferences on harmonization. guidance for industry: Impurities residual solvents, U.S. department of health and human services food and drug administration, (CDER), Q3C. Fed. Regist. 1997 1 1 1 13
    [Google Scholar]
  30. Roy J. Islam M. Khan A.H. Das S.C. Akhteruzzaman M. Deb A.K. Alam A.H.M. Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity. J. Pharm. Sci. 2001 90 5 541 544 10.1002/1520‑6017(200105)90:5<541::AID‑JPS1011>3.0.CO;2‑O 11288099
    [Google Scholar]
  31. Walker G.A. Hogerzeil H.V. Hillgren U. Potency of ergometrine in tropical countries. Lancet 1988 332 8607 393 10.1016/S0140‑6736(88)92858‑9 2899794
    [Google Scholar]
  32. Pharmacopeial Convention. United States Pharmacopeia (USP 41) Rockville, MD, USA United States Pharmacopeia 2018 1 6
    [Google Scholar]
  33. Hoq M.M. Morsheda S.B. Gomes D.J. Development of appropriate preservative system for liquid antacid: bacterial contaminants in antacid samples. J. Microbiol. 1991 8 1 5 11
    [Google Scholar]
  34. Ahuja S. Alsante K.M. Handbook of Isolation and Characterization of Impurities in Pharmaceuticals, Separation Science and Technology. San Diego, London Academic press 2003 5 430
    [Google Scholar]
  35. Ahuja S. Impurities Evaluation of Pharmaceuticals. 1st Ed. New York Marcel Dekker, Inc. 2006 304
    [Google Scholar]
  36. Ahuja S. Scypinski S. Handbook of Modern Pharmaceutical Analysis, Separation Science and Technology. San Diego, London Academic press 2003 3 566
    [Google Scholar]
  37. Roy J. ICH harmonized triplicate guideline: Impurities in new drug substances Q3A (R2), ICH steering committee, step 4 of ICH process. AAPS Pharm. Sci. Tech. 2006 3 2 1 8
    [Google Scholar]
  38. ICH harmonized triplicate guideline: Impurities in new drug products Q3B (R2), ICH steering committee, Step 4 of ICH process. Euro. Medi. Agen. 2006 12 1 20
    [Google Scholar]
  39. Görög S. Babják M. Balogh G. Brlik J. Csehi A. Dravecz F. Gasdag M. Horváth P. Laukó A. Varga K. Drug impurity profiling strategies. Talanta 1997 44 9 1517 1526 10.1016/S0039‑9140(96)02179‑0 18966892
    [Google Scholar]
  40. Orr J.D. Krull S. Swartz M.E. Validation of impurity methods, Part I. N. Am. 2003 21 7 626 633
    [Google Scholar]
  41. Orr J.D. Krull S. Swartz M.E. Validation of impurity methods. Part II. N. Am. 2003 21 12 1146 1152
    [Google Scholar]
  42. Sankar D.G. Kondaveni R. Raju T.R. Krishna M.V. Gradient stability indicating RP-HPLC method for impurity profiling of simvastatin in tablet dosage forms. Asian J. Chem. 2009 21 6 4294 4300
    [Google Scholar]
  43. Sankar D.G. Kondaveni R. Raju T.R. Krishna M.V. Impurity profiling of aspirin in tablet dosage forms by reverse phase high performance liquid chromatography. Asian J. Chem. 2009 21 6 4289 4293
    [Google Scholar]
  44. Pharmaceutical cGMPs for the 21st Century-A Risk-based Approach. Silver Spring, MD, USA Food and Drug Administration 2004 1 32
    [Google Scholar]
  45. Alsante K.M. Hatajik T. D. Lohr L. L. Isolation and identification of process related impurities and degradation products from pharmaceutical drug candidates. Part I. Am. Pharm. Rev. 2001 4 1 70 78
    [Google Scholar]
  46. Grekas N. Organic impurities in chemical drug substances. Pharma. Technol. Eur. 2005 10 7 24 32
    [Google Scholar]
  47. ICH Harmonized Triplicate Guideline: Stability Testing of New Drug Substances and Products Q1A (R2), ICH Steering Committee, Step 4 of ICH process. Euro. Medi. Agen. 2003 99 1 20
    [Google Scholar]
  48. ICH Harmonized Triplicate Guideline: Stability Testing: Photostability Testing of New Drug Substances and Products Q1B (R2), ICH Steering Committee, Step 4 of ICH process. Harmon. Tripl. 1996 4 1 12
    [Google Scholar]
  49. US-FDA Guidelines, NDAs: Impurities in New Drug Substances. Rockville, MD U.S. Food and Drugs 2000 1 3
    [Google Scholar]
  50. US-FDA Guidelines, ANDAs: Impurities in New Drug Substances. Rockville, MD U.S. Food and Drugs 2009 1 4
    [Google Scholar]
  51. Australian Regulatory Guidelines for the prescription medicines impurities in active pharmaceutical ingredients and finished products, Therapeutic Governance Authority (TGA), Australia. Guid. Resour. 2019 1 1 6
    [Google Scholar]
  52. Orr J.D. Krull S. Swartz M.E. Validation of Impurity Methods, Part I. LC GC N. Am. 2003 21 7 626 633
    [Google Scholar]
  53. Orr J.D. Krull S. Swartz M.E. Validation of Impurity Methods. Part II. LC GC N. Am. 2003 21 12 1146 1152
    [Google Scholar]
  54. Rahman N. Azmi S.N.H. Wu H.F. The importance of impurity analysis in pharmaceutical products: an integrated approach. Accredit. Qual. Assur. 2006 11 1-2 69 74 10.1007/s00769‑006‑0095‑y
    [Google Scholar]
  55. ICH Q3 Q3A(R): impurities in new drug substances (revised guideline). Fed. Regist. 2003 68 6924 6925
    [Google Scholar]
  56. Q3B(R): impurities in new drug products (revised guideline). Fed. Regist. 2003 68 220 64628 64629 14619944
    [Google Scholar]
  57. Q3C: impurities: guideline for residual solvents. Fed. Regist. 2003 68 219 64352 64353 14619948
    [Google Scholar]
  58. Skrdla P.J. Abrahim A. Wu Y. An HPLC chromatographic reactor approach for investigating the hydrolytic stability of a pharmaceutical compound. J. Pharm. Biomed. Anal. 2006 41 3 883 890 10.1016/j.jpba.2006.02.005 16524680
    [Google Scholar]
  59. Zwir-Ferenc A. Biziuk M. Solid phase extraction technique--trends, opportunities and applications. Pol. J. Environ. Stud. 2006 15 5 677 690
    [Google Scholar]
  60. Baggiani C. Anfossi L. Giovannoli C. Solid phase extraction of food contaminants using molecular imprinted polymers. Anal. Chim. Acta 2007 591 1 29 39 10.1016/j.aca.2007.01.056 17456421
    [Google Scholar]
  61. Yamasaki K. Tagami T. Kawaguchi M. Okihashi M. Takatori S. Sakagami Y. Sekita S. Satake M. Simple and rapid analysis of aristolochic acid contained in crude drugs and Kampo formulations with solid-phase extraction and HPLC photodiode-array detection. J. Nat. Med. 2009 63 4 451 458 10.1007/s11418‑009‑0353‑5 19680738
    [Google Scholar]
  62. Muller E. Berger R. Blass E. Sluyts D. Pfennig A. Liquid–liquid extraction. Ullmann's Encyclopedia of Industrial Chemistry 2008 10.1002/14356007.b03_06.pub2
    [Google Scholar]
  63. Richter B.E. Jones B.A. Ezzell J.L. Porter N.L. Avdalovic N. Pohl C. Accelerated solvent extraction: A technique for sample preparation. Anal. Chem. 1996 68 6 1033 1039 10.1021/ac9508199
    [Google Scholar]
  64. Sun H. Ge X. Lv Y. Wang A. Application of accelerated solvent extraction in the analysis of organic contaminants, bioactive and nutritional compounds in food and feed. J. Chromatogr. A 2012 1237 1 23 10.1016/j.chroma.2012.03.003 22465684
    [Google Scholar]
  65. Ashraf-Khorassani M. Taylor L.T. Waterman K.C. Narayan P. Brannegan D.R. Reid G.L. Purification of pharmaceutical excipients with supercritical fluid extraction. Pharm. Dev. Technol. 2005 10 4 507 516 10.1080/10837450500299958 16370180
    [Google Scholar]
  66. Roth M. Hampaǐ A. Column chromatography of amino acids with fluorescence detection. J. Chromatogr. A 1973 83 353 356 10.1016/S0021‑9673(00)97051‑1 4733857
    [Google Scholar]
  67. Still W.C. Clark W. Flash chromatography. United States patent US 4,1981,422,293 1981
  68. Münster-Müller S. Zimmermann R. Pütz M. A novel impurity-profiling workflow with the combination of flash-chromatography, UHPLC-MS, and multivariate data analysis for highly pure drugs: a study on the synthetic cannabinoid MDMB-CHMICA. Anal. Chem. 2018 90 17 10559 10567 10.1021/acs.analchem.8b02679 30079731
    [Google Scholar]
  69. Poole C.F. Thin-layer chromatography: challenges and opportunities. J. Chromatogr. A 2003 1000 1-2 963 984 10.1016/S0021‑9673(03)00435‑7 12877208
    [Google Scholar]
  70. Jennings W. Mittlefehldt E. Stremple P. Analytical gas chromatography. 2nd Ed San Diego Academic Press 1997 389
    [Google Scholar]
  71. Horváth C. High-Performance Liquid Chromatography: Advances and Perspectives. 1st Ed San Diego Academic Press 1980 341 10.1016/C2013‑0‑10806‑9
    [Google Scholar]
  72. Desfontaine V. Guillarme D. Francotte E. Nováková L. Supercritical fluid chromatography in pharmaceutical analysis. J. Pharm. Biomed. Anal. 2015 113 56 71 10.1016/j.jpba.2015.03.007 25818887
    [Google Scholar]
  73. Ewing A.G. Wallingford R.A. Olefirowicz T.M. Capillary electrophoresis. Anal. Chem. 1989 61 4 292A 303A 10.1021/ac00179a722 2712298
    [Google Scholar]
  74. Kempe S. Metz H. Mäder K. Application of electron paramagnetic resonance (EPR) spectroscopy and imaging in drug delivery research – Chances and challenges. Eur. J. Pharm. Biopharm. 2010 74 1 55 66 10.1016/j.ejpb.2009.08.007 19723580
    [Google Scholar]
  75. Naron D.R. Collard F.X. Tyhoda L. Görgens J.F. Characterisation of lignins from different sources by appropriate analytical methods: Introducing thermogravimetric analysis-thermal desorption-gas chromatography–mass spectroscopy. Ind. Crops Prod. 2017 101 61 74 10.1016/j.indcrop.2017.02.041
    [Google Scholar]
  76. Sautel M. Krstulović A.M. Pharmaceutical analysis beyond compendial requirements. J. Sep. Sci. 2005 28 13 1529 1538 10.1002/jssc.200400064 16158995
    [Google Scholar]
  77. Husain S. Nageswara Rao R. Monitoring of process impurities in drugs. Advanced Chromatographic and Electromigration Methods in Biosciences. Deyl Z. Miksik I. Tagliero F. Tesarova E. Amsterdam, The Netherlands Elsevier 1998 833 888 10.1016/S0301‑4770(08)60317‑6
    [Google Scholar]
  78. Alsante K.M. Friedmann R.C. Hatajik T.D. Lohr L.L. Sharp T.R. Snyder K.D. Szczesny E.J. Degradation and impurity analysis for pharmaceutical drug candidates. Handbook of Modern Pharmaceutical Analysis. Ahuja S. Scypinski S. San Diego, USA Academic Press 2001 85 172 10.1016/S0149‑6395(01)80006‑4
    [Google Scholar]
  79. Todd C. Sheinin E. Handbook of Pharmaceutical Analysis by HPLC. Ahuja S. Dong M. San Diego, USA Academic Press 2005 359 377
    [Google Scholar]
  80. Zhou L.Z. Handbook of Pharmaceutical Analysis by HPLC. Ahuja S. Dong M. San Diego, USA Academic Press 2005 499 568 10.1016/S0149‑6395(05)80063‑7
    [Google Scholar]
  81. Chin J. Fell J.B. Jarosinski M. Shapiro M.J. Wareing J.R. HPLC/NMR in combi-natorial chemistry. J. Org. Chem. 1998 63 2 386 390 10.1021/jo9713666
    [Google Scholar]
  82. Thiele H. McLeod G. Niemitz M. Kühn T. Structure verification of small molecules using mass spectrometry and NMR spectroscopy. Monatsh. Chem. 2011 142 7 717 730 10.1007/s00706‑011‑0486‑6
    [Google Scholar]
  83. Ramachandra B. Development of impurity profiling methods using modern analytical techniques. Crit. Rev. Anal. Chem. 2017 47 1 24 36 10.1080/10408347.2016.1169913 27070830
    [Google Scholar]
  84. Rao R.N. Vali R.M. Ramachandra B. Raju S.S. Separation and characterization of forced degradation products of abacavir sulphate by LC–MS/MS. J. Pharm. Biomed. Anal. 2011 54 2 279 285 10.1016/j.jpba.2010.08.021 20869185
    [Google Scholar]
  85. Ertürk S. Sevinç Aktaş E. Ersoy L. Fıçıcıoğlu S. An HPLC method for the determination of atorvastatin and its impurities in bulk drug and tablets. J. Pharm. Biomed. Anal. 2003 33 5 1017 1023 10.1016/S0731‑7085(03)00408‑4 14656592
    [Google Scholar]
  86. Sebaiy M.M. El-Shanawany A.A. Sobhy M. Abdel-Aziz L.M. Hashem H.A. Rapid RP-HPLC method for simultaneous estimation of norfloxacin and tinidazole in tablet dosage form. Asi. J. Pharma. Analy. 2011 1 4 79 84
    [Google Scholar]
  87. Siddiqui M.R. AlOthman Z.A. Rahman N. Analytical techniques in pharmaceutical analysis: A review. Arab. J. Chem. 2017 10 S1409 S1421 10.1016/j.arabjc.2013.04.016
    [Google Scholar]
  88. Pavić K. Čudina O. Agbaba D. Vladimirov S. Quantitative analysis of cyproterone acetate and ethinylestradiol in tablets by use of planar chromatography. J. Planar Chromatogr. Mod. TLC 2003 16 1 45 47 10.1556/JPC.16.2003.1.9
    [Google Scholar]
  89. Khan Z.G. Bari S.B. Gujarathi S.N. Gujarathi S.B. Patil P.B. Azilsartan: A review of analytical methods for estimation in pharmaceutical formulation. Asi. J. Pharma. Analy. 2018 8 4 227 232 10.5958/2231‑5675.2018.00041.8
    [Google Scholar]
  90. Dongre V.G. Karmuse P.P. Rao P.P. Kumar A. Development and validation of UPLC method for determination of primaquine phosphate and its impurities. J. Pharm. Biomed. Anal. 2008 46 2 236 242 10.1016/j.jpba.2007.09.012 18029132
    [Google Scholar]
  91. Plumb R. Castro Perez J. Granger J. Beattie I. Joncour K. Wright A. Ultra performance liquid chromatography coupled to quadrupole-orthogonal time of flight mass spectrometry. Rapid Commun. Mass Spectrom. 2004 18 19 2331 2337 10.1002/rcm.1627 15384155
    [Google Scholar]
  92. Meussen B.J. van Zeeland A.N.T. Bruins M.E. Sanders J.P.M. A fast and accurate UPLC method for analysis of proteinogenic amino acids. Food Anal. Methods 2014 7 5 1047 1055 10.1007/s12161‑013‑9712‑7
    [Google Scholar]
  93. Yanaka R. Gandham H.B. Rumalla C.S. Kaliyaperumal M. Saida S.J. Jammula A.R. Isolation, identification and characterization of gefitinib novel degradation products by NMR and HRMS, method development and validation by UPLC. Asian J. Chem. 2021 33 8 1743 1748 10.14233/ajchem.2021.23210
    [Google Scholar]
  94. Gorog S. Szántay C. Jr Spectroscopic methods in drug quality control and development. Encyclopedia of Spectroscopy and Spectrometry. 2nd Ed. Lindon J. Tranter G. Koppenaal D. Oxford, UK Elsevier 2010 Vol. 3 2640 2650 10.1016/B978‑0‑12‑374413‑5.00066‑X
    [Google Scholar]
  95. Szántay C. Jr Béni Z. Balogh G. Gáti T. The changing role of NMR spectroscopy in off-line impurity identification: A conceptual view. Trends Analyt. Chem. 2006 25 8 806 820 10.1016/j.trac.2006.06.006
    [Google Scholar]
  96. Szantay C. Jr Demeter A. NMR spectroscopy. Identification and Determination of Impurities in Drugs. 1st Ed. Gorog S. Amsterdam, The Netherlands Elsevier 2000 109 143 10.1016/S1464‑3456(00)80011‑3
    [Google Scholar]
  97. Aranyi A. Isolation of impurities by (semi)preparative HPLC. Identification and Determination of Impurities in Drugs. 1st Ed. Görög S. Amsterdam, The Netherlands Elsevier 2000 240 251 10.1016/S1464‑3456(00)80015‑0
    [Google Scholar]
  98. Pauli G.F. Gödecke T. Jaki B.U. Lankin D.C. Quantitative 1H NMR. Development and potential of an analytical method: An update. J. Nat. Prod. 2012 75 4 834 851 10.1021/np200993k 22482996
    [Google Scholar]
  99. Vashi D. Kumar S. Impurity identification and characterization of some anti-diabetic drugs using various analytical methods. Asi. J. Pharma. Res. 2019 9 4 243 248 10.5958/2231‑5691.2019.00039.X
    [Google Scholar]
  100. Thakur P. Thakur U. Kaushal P. Ankalgi A.D. Kumar P. Kapoor A. Singh Ashawat M. A review on GC-MS hyphenated technique. Asi. J. Pharma. Analy. 2021 11 4 285 292 10.52711/2231‑5675.2021.00049
    [Google Scholar]
  101. Akshatha H.S. Gurupadayya B.M. Application of liquid chromatography coupled with mass spectrometry in the impurity profiling of drug substances and products. Asian J. Pharm. Clin. Res. 2018 11 5 307
    [Google Scholar]
  102. Grigori K. Loukas Y.L. Malenović A. Samara V. Kalaskani A. Dimovasili E. Kalovidouri M. Dotsikas Y. Chemometrically assisted development and validation of LC–MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient. J. Pharm. Biomed. Anal. 2017 145 307 314 10.1016/j.jpba.2017.06.061 28709127
    [Google Scholar]
  103. Székely G. Henriques B. Gil M. Ramos A. Alvarez C. Design of experiments as a tool for LC–MS/MS method development for the trace analysis of the potentially genotoxic 4-dimethylaminopyridine impurity in glucocorticoids. J. Pharm. Biomed. Anal. 2012 70 251 258 10.1016/j.jpba.2012.07.006 22841555
    [Google Scholar]
/content/journals/cds/10.2174/0115748863361289250324042233
Loading
Identification and Detection of Pharmaceutical Impurities for Ensuring Safety Standard of Medicine: Hyphenated Analytical Techniques and Toxicity Measurements
Bentham Science Publishers ; https://doi.org/10.2174/0115748863361289250324042233
/content/journals/cds/10.2174/0115748863361289250324042233
/content/journals/cds/10.2174/0115748863361289250324042233
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: impurity sources ; ICH ; quality control ; Impurity profiling ; hyphenated techniques ; USFDA

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test