DEVELOPMENT AND VALIDATION OF A LC-MS /MS METHOD FOR THE QUANTITATIVE DETERMINATION OF TRAMADOL HYDROCHLORIDE
Abstract
The aim of this study was to develop and validated a highly sensitive, accurate, and precise liquid chromatography and tandem mass spectrometry (LC/MS/MS) method for quantitative analysis of tramadol (TMH) in human plasma using metoprolol tartrate as internal standard (IS). Material and methods: Quantitative analysis was done with methanol and 0.15 % formic acid in water (40:60, v/v) as the mobile phase and C18 as the stationary phase with a flow rate of 0.5 mL/min and MS as the detector. The mass spectrometer was operated in positive polarity mode. The method was validated for specificity, sensitivity, precision, accuracy, and other analytical parameters. The level of tramadol data was statistically analyzed using ANOVA at a 95% confidence level. Results: The total analytical run time was 2.5 min. The results found were satisfactory over the linear calibration range of 10-500 ng/mL for TMH. It is a simple, fast, precise and accurate liquid chromatographic method. Conclusions: The developed method can be used by scientific community for the quantification of tramadol in plasma samples from various clinical studies of different dose strengths.
References
2. Bumpus JA. Low-Dose Tramadol as an Off-Label Antidepressant: A Data Mining Analysis from the Patients’ Perspective. ACS Pharmacol Transl Sci 2020; 3(6): 1293-1303.
3. Subedi M, Bajaj S, Kumar MS, Mayur YC. An overview of tramadol and its usage in pain management and future perspective. Biomed Pharmacother 2019; 111: 443-451.
4. 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.
5. Papini JZB, Cereda CMS, Pedrazzoli Júnior J, Calafatti SA, de Araújo DR, Tofoli GR. Pharmacokinetics and pharmacodynamics evaluation of tramadol in thermoreversible gels. Biomed Res Int 2017; 2017: 5954629.
6. Pereira FJ, Rodríguez-Cordero A, López R, Robles LC, Aller AJ. Development and validation of an RP-HPLC-PDA method for determination of paracetamol, caffeine and tramadol hydrochloride in pharmaceutical formulations. Pharmaceuticals 2021; 14(5): 466 / doi: 10.3390/ph14050466.
7. Küçük A, Kadıoğlu Y. Determination of tramadol hydrochloride in ampoule dosage forms by using UV spectrophotometric and HPLC-DAD methods in methanol and water media. Farmaco 2005; 60: 163-169.
8. Baconi DL, Stan M, Abdul JE, Tuchila C, Balalau C. Determination of Tramadol in human plasma by HPLC with fluorescence detection. J Mind Med Sci 2016; 3(1): 55-64.
9. Bahrami G, Mohammadi B. Enhancement of fluorescence intensity of tramadol and its main metabolites in LC using precolumn derivatization with 9-fluorenylmethyl chloroformate. Chromatographia 2008; 68(11-12): 935-940.
10. Nagaraju P, Kodali B, Datla PV, Kovvasu SP. LC-MS/MS quantification of tramadol and gabapentin utilizing solid phase extraction. I J Anal Chem 2018; 2108: Article ID 1605950. / doi: 10.1155/ 2018/1605950.
11. Abdel-Megied AM, Badr El-din KM. Development of a novel LC–MS/MS method for detection and quantification of tramadol hydrochloride in presence of some mislabeled drugs: Application to counterfeit study. Biomed Cromatog 2019; 33(6): e4486 / doi: 10.1002/bmc.4486.
12. Abdelshakour MA, Hadad GM, Abdel Salam RA, Abo-ElMatty DM, Abdel Hameed EA. HPLC and UPLC-MS/MS methods for analyzing tramadol in 70 medicinal illegal products: Application to counterfeit study. Microchem J 2021; 161: 105823 / doi: 10.1016/j.microc.2020.105823.
13. Yilmaz B, Erdem AF, Simultaneous determination of tramadol and its metabolite in human urine by the gas chromatography-mass spectrometry method. J Chromatog Sci 2015; 53(7): 1037-1043.
14. El-Sayed 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 Chromatog B 2013; 926: 9-15.
15. Miao Y, Huan-De L, Ben-Mei C et al. Determination of metoclopramide in human plasma by LC-ESI-MS and its application to bioequivalance studies. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878(11-12): 883-887.
16. Wang X, Rytting E, Abdelrahman DR et al. Quantitative determination of famotidine in human maternal plasma, umbilical cord plasma and urine using high-performance liquid chromatography - mass spectrometry. Biomed Chromatogr 2013; 27(7): 866-873.
17. Zhou Y, Jiang J, Hu P, Wang H. A high-performance liquid chromatography-tandem mass spec-trometry method coupled with protein precipitation for determination of granisetron in human plasma and its application to a comparative pharmacokinetic study. Biomed Chromatogr 2014; 28(12): 1597-1600.
18. Li Y, Ding M, Ma J et al. Quantification of pantoprazole in human plasma using LC-MS/MS for pharmacokinetics and bioequivalence study. Eur J Drug Metab Pharmacokinet 2011; 35(3-4): 147-155.
19. Huynh NH, Tyrefors N, Ekman L, Johansson M. Determination of fentanyl in human plasma and fentanyl and norfentanyl in human urine using LC-MS/MS. J Pharm Biomed 2005; 37(5): 1095-1100.
20. Panainte AD, Vieriu M, Tantaru G, Apostu M, Bibire N. Fast HPLC Method for the determination of piroxicam and its application to stability study. Rev Chim (Bucharest) 2017; 68(4): 701-706.
21. Panainte AD, et al. RP-HPLC analysis method of bisoprolol fumarate in a new tablet formulation. Med Surg J - Rev Med Chir Soc Med Nat Iasi 2018; 122(3): 634-639.
22. Bibire N, Vieriu M, Tantaru G, et al. A New and Sensitive LC-MS/MS Method for the Determination of Clopidogrel in Human Plasma. Rev Chim (Bucharest) 2014; 65(7): 807-810.
23. Tantaru G, Vieriu M, Panainte AD. Bibire N. The Use of high-performance liquid chromatography in pharmaceutical analysis. Med Surg J - Rev Med Chir Soc Med Nat Iasi 2019; 123(1): 175-180.
24. Ardakani YH, Rouini MR. Improved liquid chromatographic method for the simultaneous determination of tramadol and its three main metabolites in human plasma, urine and saliva. J Pharml Biomed Anal 2007; 44: 1168-73.
25. Tanaka H, Naito T, Mino Y, Kawakami J. Validated determination method of tramadol and its desmethylates in human plasma using an isocratic LC-MS/MS and its clinical application to patients with cancer pain or non-cancer pain. J Pharm Health Care Sci 2016; 4; 2:25 / doi: 10.1186/s40780-016-0059-2.
26. Haage P, Kronstrand R, Carlsson B, Kugelberg FC, Josefsson M. Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS. J Pharm Biomed Anal 2016; 119: 1-9.
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