Qualitative and quantitative analysis of some tramadol registered and illegitimate dosage forms in Egypt
Mandour, H., Belal, T., Ramadan, A., Sharabi, F., Shamseddeen, M. (2024). Qualitative and quantitative analysis of some tramadol registered and illegitimate dosage forms in Egypt. EKB Journal Management System, 1(1), 11-21. doi: 10.21608/japs.2024.255337.1011
Hebat-ALLAH I. Mandour; Tarek S. Belal; Alyaa A. Ramadan; Fouad M. Sharabi; Mohamed A. Shamseddeen. "Qualitative and quantitative analysis of some tramadol registered and illegitimate dosage forms in Egypt". EKB Journal Management System, 1, 1, 2024, 11-21. doi: 10.21608/japs.2024.255337.1011
Mandour, H., Belal, T., Ramadan, A., Sharabi, F., Shamseddeen, M. (2024). 'Qualitative and quantitative analysis of some tramadol registered and illegitimate dosage forms in Egypt', EKB Journal Management System, 1(1), pp. 11-21. doi: 10.21608/japs.2024.255337.1011
Mandour, H., Belal, T., Ramadan, A., Sharabi, F., Shamseddeen, M. Qualitative and quantitative analysis of some tramadol registered and illegitimate dosage forms in Egypt. EKB Journal Management System, 2024; 1(1): 11-21. doi: 10.21608/japs.2024.255337.1011

Qualitative and quantitative analysis of some tramadol registered and illegitimate dosage forms in Egypt

Journal of Advanced Pharmaceutical Sciences
Volume 1, Issue 1, January 2024, Page 11-21  XML PDF (510.13 K)
Document Type: Original Article
DOI: 10.21608/japs.2024.255337.1011
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Authors
Hebat-ALLAH I. Mandour email 1; Tarek S. Belal2; Alyaa A. Ramadan3; Fouad M. Sharabi4; Mohamed A. Shamseddeen3
1Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
2Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
3Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
Abstract
Despite tramadol is a strong pain relief authorized medication, it is currently considered among the highly abused substances in Egypt. Due to consequent strict legal acts on the registered brands of tramadol, available illegitimate products were widely distributed on the streets in Egypt. The claim of many patients receiving treatment while suffering from seizures together with the assumption of inferior authenticity of these products, led the initiative to work on the qualitative and quantitative analysis of such products while comparing their content to the registered brands in the Egyptian market. Results obtained by applying a validated HPLC-DAD method as a highly efficient technique in pharmaceutical analysis revealed that most of the content of these products was within the limit of the labelled claim, with the exception of one compound that showed an additional different peak. Efforts to identify such a peak through analysis and comparison of the spectrum referred it to paracetamol, the well-known analgesic commonly combined with tramadol in its dosage forms. The employed HPLC procedure involved the use of a RP-C18 column, mobile phase of phosphate buffer (pH 6.0) and methanol (40:60, v/v) and diode array detection at 220 and 270 nm. Accurate, precise, and reliable testing procedures under governmental surveillance are required to assure the persistent quality and safety of the available drugs on the market.

Highlights
  • An HPLC-DAD adopted method was successful for the analysis of Tramadol-registered and illegitimate dosage forms in Egypt.
  • Most analyzed tramadol illegitimate dosage forms showed acceptable content recovery.
  • Only one extra peak for co-formulated paracetamol in a single tramadol illegitimate dosage form was identified within the selected detection wavelength.
  • Seizures occur with tramadol use in doses higher than therapeutically recommended and not as assumed due to other concomitantly added adulterants.
  • Pharmacists play an integral part in the surveillance of illegitimate dosage forms to protect society.
Keywords
Tramadol use; illegitimate products; counterfeit; HPLC
References
  1. Richardson CF. Compendial Testing. In: Handbook of Modern Pharmaceutical Analysis (Ahuja S, Scypinski S. eds.) Academic Press, USA; 2001 Jul 26:325-44.
  2. Martins JM, Farinha A. Uniformity of dosage units: comparative study of methods and specifications between Eur. Pharm. 3rd and USP 23. Journal of pharmaceutical and biomedical analysis. 1998 Dec 1;18(4-5):487-95.
  3. Deisingh AK. Pharmaceutical counterfeiting. Analyst. 2005; 130(3):271-9.
  4. Deconinck E, Sacré PY, Courselle P, De Beer JO. Chromatography in the detection and characterization of illegal pharmaceutical preparations. Journal of chromatographic science. 2013 Sep 1;51(8):791-806.
  5. Watson DG. Pharmaceutical Analysis: A textbook for pharmacy students and pharmaceutical chemists, 3rd Churchill Livingstone, UK; 2012:440pp.
  6. Rasmussen HT. Method Development. In: Handbook of Modern Pharmaceutical Analysis (Ahuja S, Scypinski S. eds.) Academic Press, USA; 2001 Jul 26:345-86.
  7. Patel J, Patel P. RP-HPLC method development and validation for the estimation of diclofenac sodium, tramadol hydrochloride and chlorzoxazone from their combined tablet dosage form. International Journal of Pharmacy and Pharmaceutical Sciences. 2014; 6(7):632-7.
  8. Belal T, Awad T, Clark R. Determination of paracetamol and tramadol hydrochloride in pharmaceutical mixture using HPLC and GC-MS. Journal of chromatographic science. 2009 Nov 1; 47(10):849-54.
  9. Chandra P, Rathore AS, Lohidasan S, Mahadik Application of HPLC for the simultaneous determination of aceclofenac, paracetamol and tramadol hydrochloride in pharmaceutical dosage form. Scientia pharmaceutica. 2012 Jun; 80(2):337-51.
  10. Desireddy RB, Kumar PJ, Chand AS, et al. Development and validation of RP-HPLC method for quantitative analysis of tramadol in pure and pharmaceutical formulations. International Journal of Chemical Sciences. 2012; 10(4):2039-47.
  11. Gharge D, Dhabale P. Simultaneous estimation of tramadol hydrochloride and paracetamol by UV spectrophotometric method from tablet formulation. International Journal of PharmTech Research. 2010;2(2):1119-23.
  12. Kambl RM, Singh SG. Stability-indicating RP-HPLC method for analysis of paracetamol and tramadol in a pharmaceutical dosage form. E-Journal of Chemistry. 2012 Jan 1;9(3):1347-56.
  13. Shukla R, Shivkumar R, Shivan KN. Development of a UV-spectrophotometric method for the simultaneous determination of tramadol hydrochloride and paracetamol in bulk and marketed product. Bulletin of Pharmaceutical Research. 2011;1(1):62-6.
  14. Setty KN, Ramachar T, Chakravarthy IE, Prabhavathi K. A simple spectrophotometric estimation of tramadol hydrochloride in pharmaceutical formulations. Chemical Science Transactions. 2012;1(2),317-20.
  15. Salmerón-García A, Navas N, Martín A, Román E, et al. Determination of tramadol, metamizole, ropivacaine, and bupivacaine in analgesic mixture samples by HPLC with DAD detection. Journal of chromatographic science. 2009 Mar 1;47(3):231-7.
  16. Dhillon S. Tramadol/paracetamol fixed-dose combination: a review of its use in the management of moderate to severe pain. Clinical drug investigation. 2010 Oct;30(10):711-38.
  17. Nna VU, Osim EE. Testicular toxicity following separate and combined administration of PDE5 inhibitors and opioid: Assessment of recovery following their withdrawal. Andrologia. 2017 Aug;49(6):e12669
  18. Nakhaee S, Farrokhfall K, Miri-Moghaddam E, et al. The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: an experimental study. Behavioral and Brain Functions. 2021 May 29;17(1):5.
  19. Radbruch L, Glaeske G, Grond S, et al. Topical review on the abuse and misuse potential of tramadol and tilidine in Germany. Substance abuse. 2013 Jul;34(3):313-20.
  20. Raffa RB, Stone DJ. Unexceptional seizure potential of tramadol or its enantiomers or metabolites in mice. Journal of pharmacology and experimental therapeutics. 2008 May 1;325(2):500-6.
  21. Beyaz SG, Sonbahar T, Bayar F, Erdem AF. Seizures associated with low-dose tramadol for chronic pain treatment. Anesthesia, essays and researches. 2016 May;10(2):376-8.
  22. Hassamal S, Miotto K, Dale W, Danovitch I. Tramadol: understanding the risk of serotonin syndrome and seizures. The American journal of medicine. 2018 Nov 1;131(11):1382-e1.
  23. Afshari R, Afshar R, Mégarbane B. Tramadol overdose: review of the literature. Médecine Intensive Réanimation. 2011 Aug 25;20(5):436-41.
  24. Abadinsky H. Drug use and abuse: A comprehensive introduction. 7th Wadsworth, Cengage Learning, Belmont, USA; 2011:475pp.
  25. United Nations Office on Drugs and Crime. World Drug Report 2020. United Nationspublication, accessed 20 February2020, https://wdr.unodc.org/wdr2020/en/index2020.html
  26. Sabry NA, Rabie MA, Sedrak AE, Khafagy WE. The National Research on Addiction. 1st General Secretariat of Mental Health and Addiction Treatment, MoHP, Cairo, Egypt; 2015:80pp.
  27. Shamloul RM, Elfayomy NM, Ali EI, et al. Tramadol-associated seizures in Egypt: Epidemiological, clinical, and radiological study. Neurotoxicology. 2020 Jul;79:122-6.
  28. USP U. Pharmacopoeia-national formulary [USP 38 NF 33]. Rockville, Md United States Pharmacopeial Convention. 2015.
  29. British Pharmacopoeia Commission. British Pharmacopeia 2016: volume III. London:TSO; 2016.
  30. Martyn-St James M, Cooper K, Kaltenthaler E, et al. Tramadol for premature ejaculation: a systematic review and meta-analysis. BMC urology. 2015 Dec; 15:6.
  31. Xin ZC, Zhu YC, Yuan YM, et al. Current therapeutic strategies for premature ejaculation and future perspectives. Asian Journal of Andrology. 2011 Jul;13(4):550-57.
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