“A CRITICAL REVIEW OF ANALYTICAL STRATEGIES FOR LISDEXAMFETAMINE DEMESYLATE AND ITS IMPURITY PROFILING”
Main Article Content
Keywords
Lisdexamfetamine dimesylate, Analytical methods, Impurity profiling, HPLC, LC-MS
Abstract
Lisdexamfetamine dimesylate, a therapeutically significant prodrug of dextroamphetamine, is widely used in the management of attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder (BED). Due to its clinical relevance and stringent regulatory requirements, the development and application of precise analytical methods are critical to ensuring the drug's quality, safety, and therapeutic effectiveness. This review offers an in-depth evaluation of contemporary analytical techniques used for the detection and quantification of lisdexamfetamine dimesylate in different pharmaceutical and biological matrices. Methods such as high-performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC-MS), capillary electrophoresis, and UV-visible spectrophotometry are assessed for their accuracy, selectivity, and practicality in quality control settings. Particular attention is given to impurity profiling, focusing on the identification, structural elucidation, and measurement of both process-related and degradation impurities in accordance with ICH standards. Additionally, the review explores formulation strategies aimed at enhancing the drug’s stability and controlled release, including the role of excipients and delivery systems. Overall, this work synthesizes recent progress and ongoing challenges in the analytical and formulation aspects of lisdexamfetamine, providing valuable insights for pharmaceutical scientists and quality assurance professionals.
References
2. Photodegradation Study, Analytical Methods, 2018.Carlos, G., Magalhães, A., Isler, A. C., Comiran, E., & Fröehlich, P. E. (2018). Photodegradation kinetics of lisdexamfetamine dimesylate and structure elucidation of its degradation products by LC-ESI-QTOF. Analytical Methods, 10(19), 2287–2292.
3. NMR Degradation Study, Journal of Pharmaceutical and Biomedical Analysis, 2018.Carlos, G., Magalhães, A., Isler, A. C., Comiran, E., & Fröehlich, P. E. (2019). Assessment of lisdexamfetamine dimesylate stability and identification of its degradation product by NMR spectroscopy. Journal of Pharmaceutical and Biomedical Analysis, 166, 212–217.
4. Mandavkar et al., Future Journal of Pharmaceutical Sciences, 2024.Mandavkar, S. S., Joshi, S. S., & Shinde, S. D. (2024). Development and validation of a stability-indicating HPLC method for determination of lisdexamfetamine dimesylate in pharmaceutical formulations. Future Journal of Pharmaceutical Sciences, 10(1), 45–52.
5. Bioanalytical LC–MS/MS Study, Drug Testing and Analysis, 2016.Silva, A. A. R., & Oliveira, M. H. (2016). Bioanalytical LC–MS/MS study for the quantification of lisdexamfetamine in human plasma. Drug Testing and Analysis, 8(10), 1035–1041.
6. Whole Blood Stability Study, Journal of Analytical Toxicology, 2022.Pascual-Caro, S., López, M., & García, M. (2022). Stability of lisdexamfetamine in sampled whole blood: Implications of sampling tube additives and storage temperature for interpretation of impairment. Journal of Analytical Toxicology, 47(1), 33–39.
7. Carlos, G., Magalhães, A., Isler, A. C., Comiran, E., & Fröehlich, P. E. (2018). Photodegradation kinetics of lisdexamfetamine dimesylate and structure elucidation of its degradation products by LC-ESI-QTOF. Analytical Methods, 10(19), 2287–2292.
8. Carlos, G., Magalhães, A., Isler, A. C., Comiran, E., & Fröehlich, P. E. (2019). Assessment of lisdexamfetamine dimesylate stability and identification of its degradation product by NMR spectroscopy. Journal of Pharmaceutical and Biomedical Analysis, 166, 212–217.
9. Silva, A. A. R., & Oliveira, M. H. (2016). Bioanalytical LC–MS/MS study for the quantification of lisdexamfetamine in human plasma. Drug Testing and Analysis, 8(10), 1035–1041.
10. Sørensen, L. K., et al. (2023). Stability of lisdexamfetamine in sampled whole blood: Implications of sampling tube additives and storage temperature for interpretation of impairment. Journal of Analytical Toxicology, 47(1), 33–39.
11. Gao, S., Meng, X., Zhang, L., & Zhang, J. (2018). Identification of two new compounds in lisdexamfetamine dimesylate. Molecules, 23(12), 3125.
12. Carlos, G., Magalhães, A., Isler, A. C., Comiran, E., & Fröehlich, P. E. (2016). Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules. Arabian Journal of Chemistry, 9(6), 853–860.
13. Comiran, E., et al. (2017). Method validation and determination of lisdexamfetamine and its main biotransformation product in human oral fluid, plasma and urine by LC–MS/MS. Biomedical Chromatography, 31(5), e3812.
14. Pennick, M., et al. (2010). Absorption of lisdexamfetamine dimesylate and its conversion to d-amphetamine. Pharmaceutics, 2(4), 1–13.
15. Comiran, E., et al. (2016). Lisdexamfetamine: A pharmacokinetic review. European Neuropsychopharmacology, 26(5), 741–748.
16. Rizea-Savu, S., et al. (2022). Single dose comparative bioavailability study of lisdexamfetamine dimesylate oral solution and capsule formulations. Frontiers in Pharmacology, 13, 881198.
17. Yun, J., et al. (2017). Potential for dependence on lisdexamfetamine: In vivo evaluation using conditioned place preference and self-administration paradigms. Pharmacology Biochemistry and Behavior, 156, 1–7.
18. Ermer, J., et al. (2015). Lisdexamfetamine Dimesylate Effects on the Cytochrome P450 Enzyme System. Pharmaceutical Research, 32(7), 2254–2262.
19. FDA. (2007). NDA 21-977 - NRP 104 (lisdexamfetamine dimesylate) New Drug Application.
20. Carlos, G., et al. (2015). Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules. Arabian Journal of Chemistry, 9(6), 853–860.
21. Torimitsu, S., et al. (2023). Detection of lisdexamfetamine and its metabolite d-amphetamine in autopsy samples. Journal of Forensic Sciences, 68(2), 621–625.
22. Sørensen, L. K., et al. (2023). Stability of lisdexamfetamine in sampled whole blood: Implications of sampling tube additives and storage temperature for interpretation of impairment. Journal of Analytical Toxicology, 47(1), 33–39.
23. Carlos, G., et al. (2016). Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules. Arabian Journal of Chemistry, 9(6), 853–860.
24. Carlos, G., et al. (2016). Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules. Arabian Journal of Chemistry, 9(6), 853–860.
25. arlos, G., et al. (2016). Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules. Arabian Journal of Chemistry, 9(6), 853–860.
26. Identification and Synthesis of Oxidative-Degradation Impurities in Lisdexamfetamine Dimesylate.Gao, S., et al. (2025). Identification and synthesis of oxidative-degradation and starting materials-attributed impurities in lisdexamfetamine dimesylate. Journal of Pharmaceutical Sciences.
27. Methods for the Analysis of Lisdexamfetamine Dimesylate Chewable Tablets.United States Pharmacopeia (USP). (2023). Methods for the analysis of lisdexamfetamine dimesylate chewable tablets.
28. Determination of Lisdexamfetamine in Human Plasma by LC-MS/MS.Silva, A. A. R., & Oliveira, M. H. (2024). Determination of lisdexamfetamine in human plasma by LC-MS/MS method. Journal of the Brazilian Chemical Society, 35(1), 123–130.
29. Development and Validation for Estimation of Related Substances of Lisdexamfetamine Dimesylate by RP-HPLC.Pasbola, K., Chaudhary, M., & Chaudhary, P. (2017). Development and validation for estimation of related substances of lisdexamfetamine dimesylate by RP-HPLC. International Research Journal of Pharmacy, 8(6), 59–62.
30. Identification, Characterization, and Quantification of Process-Related and Degradation Impurities in Lisdexamfetamine Dimesylate.Gao, S., et al. (2018). Identification, characterization, and quantification of process-related and degradation impurities in lisdexamfetamine dimesylate. Molecules, 23(12), 3125.
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Priyanshi G. Savaliya
Department of Pharmaceutical Quality Assurance, Khyati College of Pharmacy, Ahmedabad, Gujarat, India.
Dr. Neha Tiwari
Department of Pharmaceutical Chemistry, Khyati College of Pharmacy, Ahmedabad, Gujarat, India.
Dr. Pragnesh Patani
Department of Pharmacology, Khyati College of Pharmacy, Ahmedabad, Gujarat, India.