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AAPS PharmSciTech. 2002 June; 3(2): 1–8.
Published online 2002 March 8. doi:  10.1208/pt030206
PMCID: PMC2750308

Pharmaceutical impurities—A mini-review


The control of pharmaceutical impurities is currently a critical issue to the pharmaceutical industry. The International Conference on Harmonization (ICH) has formulated a workable guideline regarding the control of impurities. In this review, a description of different types and origins of impurities in relation to ICH guidelines and, degradation routes, including specific examples, are presented. The article further discusses measures regarding the control of impurities in pharmaceuticals

Key words: Bulk drugs, impurities, formulation, drug stability, degradation

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. International Conferences on Harmonization, Draft Revised Guidance on Impurities in New Drug Substances. Q3A(R). Federal Register. 2000;65(140):45085–45090.
2. International Conferences on Harmonization, Draft Revised Guidance on Impurities in New Drug Products. Q3B(R). Federal Register. 2000;65(139):44791–44797.
3. International Conferences on Harmonization, Impurities--Guidelines for Residual Solvents. Q3C. Federal Register. 1997;62(247):67377.
4. Ahuja S. Impurities Evaluation of Pharmaceuticals. New York: Marcel Dekker; 1998.
5. Gorog S. Identification and Determination of Impurities in Drugs. Amsterdam: Elsevier Science Publishing Company; 2000.
6. Alsante KM, Hatajik TD, Lohr LL, Sharp TR. Isolation and identification of process related impurities and degradation products from pharmaceutical drug candidates. Part 1. American Pharmaceutical Review. 2001;4(1):70–78.
7. Lohr LL, Sharp TR, Alsante KM, and Hatajik TD. Isolation and identification of process related impurities and degradation products from pharmaceutical drug candidates. Part II: The roles of NMR and mass spectrometry. American Pharmaceutical Review. Fall issue 2001; Available at: icles_f.htm.
8. Winger BE, Kemp CAJ. Characterization of pharmaceutical compounds and related substances by using HPLC FTICR-MS and tandem mass spectrometry. American Pharmaceutical Review. Summer issue 2001; Available at: http://www.americanpharma
9. Van Krimpen PC, Van Bennekom WP, Bult A. Penicillins and cephalosporins: physicochemical properties and analysis in pharmaceutical and biological matrices. Pharm Weekbl [Sci] 1987;9:1–23. [PubMed]
10. Roy J., Mohammad G., Banu A. Pharmaceutical analysis and stability of locally manufactured ampicillin trihydrate. Indian Drugs. 1993;5(30):211–218.
11. Pharmacopoeia British. The British Pharmacopoeia Commission, Vol. 1. London, UK: The Stationary Office; 2001. pp. 123–123.
12. Riley TN. Steric aspects of drug action. US Pharmacist. 1998;23(3):40–51.
13. Roy J, Islam M., Khan AH, Das SC, Akhteruzzaman M, Deb AK, Alam AHM. 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. doi: 10.1002/1520-6017(200105)90:5<541::AID-JPS1011>3.0.CO;2-O. [PubMed] [Cross Ref]
14. Walker GJA, Hogerzeil HV, Hillgreen U. Potency of ergometrine in tropical countries. Lancet. 1988;2:393–393. doi: 10.1016/S0140-6736(88)92858-9. [PubMed] [Cross Ref]
15. Hogerzeil HV, Battersby A, Srdanovic V, Stjernstrom NE. Stability of essential drugs during shipment to the tropics. BMJ. 1992;304:210–214. [PMC free article] [PubMed]
16. Roy J, Bhuiyan K, Faruque A., Sobahan M., Al-Farooque M. Injectable ergometrine: stability and packaging for developing countries. Indian Drugs. 1997;34(11):634–636.
17. Food and Drug Administration for immediate release consumer media: 888-Info.-FDA. May 6, 1998.
18. Hoq MM, Morsheda SB, Gomes DJ. Development of approapriate preservative system for liquid antacid: bacterial contaminants in antacid samples. Bang J Microbiology. 1991;8(1):5–9.
19. Buhler V. Vademecum for Vitamin Formulation. Stuttgart, Germany: Wiss. Verl-Ges; 1988.
20. Roy J, Mahmud M, Sobhan A, Aktheruzzaman M, Al-Faooque M, Ali E. Marketed vitamin B-complex injectables: stability and mutual interaction. Drug Dev. and Ind Pharm. 1994;20(13):2157–2163. doi: 10.3109/03639049409050229. [Cross Ref]
21. Connor KA, Amidon GL, Stella VJ. Chemical Stability of Pharmaceuticals-A Handbook for Pharmacists. New York: John Wiley & Sons; 1986.
22. Hoerle SL, Evans KD, and Snider BG. HPLC Determination of Impurities in a 3rd Generation Cephalosporin. Eastern Analytical Symposium. November 16–20, 1992, Somerset, New Jersey.
23. Kumar V, Sunder N, Potdar A. Critical factors in developing pharmnaceutical formulations- An overview. Part II. Pharmaceutical Technology. 1992;16:86–88.
24. Smith A, Pennefather PM, Kaye SB, Hart CA, CA Fluoroquinolones—place in ocular therapy. Drugs. 2001;61(6):747–761. doi: 10.2165/00003495-200161060-00004. [PubMed] [Cross Ref]
25. Tobin C. Sunlight, eyes and light-sensitive antibiotics, Southmead Hospital Bristol, University of Bristol. Available at: Accessed October 27, 2001.
26. Sunderland J, Tobin CM, White LO, MacGowan AP, Hedges AJ. Ofloxacin photodegradation products possess antimicrobial activity. Drugs. 1999;58(Suppl 2):171–172. doi: 10.2165/00003495-199958002-00048. [Cross Ref]
27. Roy J, Das SC. The effect of sunglight on ciprofloxacin eye drops. In press.
28. Condorelli G., De Guidi G, Giulfrido S, Sortino S, Chilleni R, Sciuto 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. Photochemistry & Photobiology. 1999;70(3):280–286. doi: 10.1111/j.1751-1097.1999.tb08136.x. [PubMed] [Cross Ref]

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