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Journals / NanoEra / 2026 / Volume: 5 Issue: 1

Determination of tramadol in pharmaceutical preparations by GC-MS method

Bilal Yılmaz(ATATURK UNIVERSITY)0000-0002-8574-7570
Emrah Alkan(ATATURK UNIVERSITY)0000-0002-0020-7170
Journal
NanoEra
Pages
—
Publication Date
2025-06-25
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AI Summary & Key Takeaways

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⚡ TL;DR(Too Long; Didn't Read)

Furthermore, the method proved to be effective in quantifying tramadol and ensuring the consistency of formulation content in commercial tramadol dosage forms.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:In this study, a gas chromatography-mass spectrometry (GC-MS) method was developed to analyze tramadol in both pure form and pharmaceutical formulations.
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Key Findings & Data:The linearity of the GC-MS method was validated within a concentration range of 0.05-5.0 μg mL-1.
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Conclusion & Impact:Furthermore, the method proved to be effective in quantifying tramadol and ensuring the consistency of formulation content in commercial tramadol dosage forms.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Tramadol · GC-MS · Validation

Abstract

In this study, a gas chromatography-mass spectrometry (GC-MS) method was developed to analyze tramadol in both pure form and pharmaceutical formulations. Diclofenac served as the internal standard. The linearity of the GC-MS method was validated within a concentration range of 0.05-5.0 μg mL-1. The intra- and inter-day relative standard deviations were found to be below 1.18% and 3.51%, respectively. The detection and quantification limits for the GC-MS method were determined to be 0.015 and 0.045 μg mL-1, respectively. Stability testing revealed that tramadol remained stable in solutions after 24 hours of incubation at room temperature or after 72 hours of storage at 4 °C and -20°C. Under the selected assay conditions, tablet excipients did not cause any interference. Furthermore, the method proved to be effective in quantifying tramadol and ensuring the consistency of formulation content in commercial tramadol dosage forms.

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Cite This Article

Yılmaz, B., Alkan, E. (2025). Determination of tramadol in pharmaceutical preparations by GC-MS method. NanoEra, Volume: 5 Issue: 1. https://doi.org/10.5281/zenodo.15729141

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References (31)

  1. Gibson TP. Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. Am J Med. 1996;101:S47-S53. doi:10.1016/S0002-9343(96)00138-6
  2. Shipton EA. Tramadol—Present and Future. Anaesth Intensive Care. 2000;28(4):363-374. doi:10.1177/0310057X0002800403
  3. Cooper RJ. Over-the-counter medicine abuse – a review of the literature. J Subst Use. 2013;18(2):82-107. doi:10.3109/14659891.2011.615002
  4. Almér Herrnsdorf E, Holmstedt A, Håkansson A. Tramadol misuse in treatment-seeking adolescents and young adults with problematic substance use – Prediction of treatment retention. Addict Behav Reports. 2022;16:100446. doi:10.1016/j.abrep.2022.100446
  5. Miotto K, Cho AK, Khalil MA, Blanco K, Sasaki JD, Rawson R. Trends in Tramadol: Pharmacology, Metabolism, and Misuse. Anesth Analg. 2017;124(1):44-51. doi:10.1213/ANE.0000000000001683
  6. Allegaert K, Anderson BJ, Verbesselt R, et al. Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P -450 2D6 activity. Br J Anaesth. 2005;95(2):231-239. doi:10.1093/bja/aei170
  7. Goeringer KE, Logan BK, Christian GD. Identification of Tramadol and its Metabolites in Blood from Drug-Related Deaths and Drug-Impaired Drivers. J Anal Toxicol. 1997;21(7):529-537. doi:10.1093/jat/21.7.529
  8. Quetglas EG, Azanza JR, Cardenas E, Sádaba B, Campanero MA. Stereoselective pharmacokinetic analysis of tramadol and its main phase I metabolites in healthy subjects after intravenous and oral administration of racemic tramadol. Biopharm Drug Dispos. 2007;28(1):19-33. doi:10.1002/bdd.526
  9. Ardakani YH, Rouini M. Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers. Biopharm Drug Dispos. 2007;28(9):527-534. doi:10.1002/bdd.584
  10. El-Sayed A-AY, Mohamed KM, Nasser AY, Button J, Holt DW. Simultaneous determination of tramadol, O-desmethyltramadol and N-desmethyltramadol in human urine by gas chromatography–mass spectrometry. J Chromatogr B. 2013;926:9-15. doi:10.1016/j.jchromb.2013.02.019
  11. Ghasemi E. Optimization of solvent bar microextraction combined with gas chromatography mass spectrometry for preconcentration and determination of tramadol in biological samples. J Chromatogr A. 2012;1251:48-53. doi:10.1016/j.chroma.2012.06.060
  12. Sha YF, Shen S, Duan GL. Rapid determination of tramadol in human plasma by headspace solid-phase microextraction and capillary gas chromatography–mass spectrometry. J Pharm Biomed Anal. 2005;37(1):143-147. doi:10.1016/j.jpba.2004.09.050
  13. Rudaz S, Veuthey JL, Desiderio C, Fanali S. Simultaneous stereoselective analysis by capillary electrophoresis of tramadol enantiomers and their main phase I metabolites in urine. J Chromatogr A. 1999;846(1-2):227-237. doi:10.1016/S0021-9673(99)00028-X
  14. Valle M, Pavón J., Calvo R, Campanero M., Trocóniz I. Simultaneous determination of tramadol and its major active metabolite O-demethyltramadol by high-performance liquid chromatography with electrochemical detection. J Chromatogr B Biomed Sci Appl. 1999;724(1):83-89. doi:10.1016/S0378-4347(98)00547-7
  15. Ceccato A, Vanderbist F, Pabst J-Y, Streel B. Enantiomeric determination of tramadol and its main metabolite O-desmethyltramadol in human plasma by liquid chromatography–tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 2000;748(1):65-76. doi:10.1016/S0378-4347(00)00318-2
  16. Musshoff F, Madea B, Stuber F, Stamer UM. Enantiomeric Determination of Tramadol and O-Desmethyltramadol by Liquid Chromatography-Mass Spectrometry and Application to Postoperative Patients Receiving Tramadol. J Anal Toxicol. 2006;30(7):463-467. doi:10.1093/jat/30.7.463
  17. Musshoff F, Trafkowski J, Kuepper U, Madea B. An automated and fully validated LC‐MS/MS procedure for the simultaneous determination of 11 opioids used in palliative care, with 5 of their metabolites. J Mass Spectrom. 2006;41(5):633-640. doi:10.1002/jms.1021
  18. Zhu T, Ding L, Guo X, Yang L, Wen A. Simultaneous Determination of Tramadol and Acetaminophen in Human Plasma by LC–ESI–MS. Chromatographia. 2007;66(3-4):171-178. doi:10.1365/s10337-007-0268-9
  19. Campanero MA, Calahorra B, García-Quetglás E, Escolar M, Honorato J. High-performance liquid chromatographic assay for simultaneous determination of tramadol and its active metabolite in human plasma. Application to pharmacokinetic studies. Chromatographia. 1998;48(7-8):555-560. doi:10.1007/BF02466649
  20. Nobilis M, Kopecký J, Květina J, et al. High-performance liquid chromatographic determination of tramadol and its O-desmethylated metabolite in blood plasma. J Chromatogr A. 2002;949(1-2):11-22. doi:10.1016/S0021-9673(01)01567-9
  21. Campanero MA, Garcı́a-Quetglas E, Sádaba B, Azanza JR. Simultaneous stereoselective analysis of tramadol and its primary phase I metabolites in plasma by liquid chromatography. J Chromatogr A. 2004;1031(1-2):219-228. doi:10.1016/j.chroma.2003.11.034
  22. Pedersen RS, Brøsen K, Nielsen F. Enantioselective HPLC method for quantitative determination of tramadol andO-desmethyltramadol in plasma and urine: Application to clinical studies. Chromatographia. 2003;57(5-6):279-285. doi:10.1007/BF02492397
  23. Rouini M-R, Ardakani YH, Soltani F, Aboul-Enein HY, Foroumadi A. Development and validation of a rapid HPLC method for simultaneous determination of tramadol, and its two main metabolites in human plasma. J Chromatogr B. 2006;830(2):207-211. doi:10.1016/j.jchromb.2005.10.039
  24. LI Q, Wang R. Simultaneous analysis of tramadol, metoprolol and their metabolites in human plasma and urine by high performance liquid chromatography. Chin Med J (Engl). 2006;119(23). https://journals.lww.com/cmj/fulltext/2006/12010/simultaneous_analysis_of_tramadol,_metoprolol_and.12.aspx
  25. Validation of analytical procedures: Text and Methodology. In: International Conference on Harmonization (ICH). Commission of the European Communities. Vol 2.; 1996.
  26. Gan S., Ismail R. Validation of a high-performance liquid chromatography method for tramadol and o-desmethyltramadol in human plasma using solid-phase extraction. J Chromatogr B Biomed Sci Appl. 2001;759(2):325-335. doi:10.1016/S0378-4347(01)00237-7
  27. Ardakani YH, Rouini M-R. Improved liquid chromatographic method for the simultaneous determination of tramadol and its three main metabolites in human plasma, urine and saliva. J Pharm Biomed Anal. 2007;44(5):1168-1173. doi:10.1016/j.jpba.2007.04.012
  28. Moore C, Rana S, Coulter C. Determination of meperidine, tramadol and oxycodone in human oral fluid using solid phase extraction and gas chromatography–mass spectrometry. J Chromatogr B. 2007;850(1-2):370-375. doi:10.1016/j.jchromb.2006.12.008
  29. Cheng P-S, Lee C-H, Liu C, Chien C-S. Simultaneous Determination of Ketamine, Tramadol, Methadone, and their Metabolites in Urine by Gas Chromatography-Mass Spectrometry. J Anal Toxicol. 2008;32(3):253-259. doi:10.1093/jat/32.3.253
  30. Chytil L, Štícha M, Matoušková O, Perlík F, Slanař O. Enatiomeric determination of tramadol and O-desmethyltramadol in human urine by gas chromatography–mass spectrometry. J Chromatogr B. 2009;877(20-21):1937-1942. doi:10.1016/j.jchromb.2009.04.042
  31. Validation of analytical procedures: Text and Methodology. In: International Conference on Harmonization (ICH). Commission of the European Communities. Vol 2.; 1996.