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Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market

(2018) TALANTA. 188. p.795-807
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Abstract
Advances in biotechnology and the chemical synthesis of peptides have made biopharmaceuticals and synthetic peptide drugs viable pharmaceutical compounds today and an important source for tomorrow's drugs and therapies. Unfortunately, also falsifications and counterfeit versions of these powerful and promising drugs are offered illegally via the intemet. Since these falsified preparations are produced outside the legally required quality systems, end-users have no guarantee regarding the efficacy and safety of these products. Although falsified samples of biotherapeutics were already analysed, looking at a specific aspect of their quality or identity, no systematic studies have been performed regarding the presence of different impurities or possible contaminations. Therefore, in order to obtain a better understanding of the potential health risks related to the usage of falsified polypeptide drugs we performed a systematic screening of the ten most frequently encountered falsified peptide drugs on the Belgian market acquired from three different suspected illegal internet pharmacies. The screening incorporated the analysis of the active pharmaceutical ingredient (API), API-related impurities, small molecule contaminants (defined as organic small molecules not belonging to the other categories), elemental impurities and residual solvents. This comprehensive study showed that these type of falsified drugs not only have a high variation in amount of drugs per unit and a low purity (ranging between 5% and 75% for cysteine containing peptides), but also contained the known toxic class one elemental impurities arsenic (As) and lead (Pb). One sample was contaminated with Pb while multiple samples were found with concentrations up to ten times the ICH toxicity limit for parenteral drugs. Subsequent speciation of As confirmed the elevated concentrations for As and demonstrated that all As was present in the more toxic inorganic form. Together with the (sometimes) high amount of peptide impurities and the inherent dangers associated with the use of unauthorized peptide drugs (such as doping peptides or preclinical drugs) this study confirms the reported potential health risks patients/users take when resorting to falsified peptide drugs. Moreover, the presence of the carcinogen As and the known accumulation in human tissues of Pb raises questions about potential sub-acute to chronic toxicity due to the long term administration of these falsified peptide drugs.
Keywords
Falsified medicines, Peptide drugs, Heavy metals, Impurity profiling, Mass spectrometry, PHASE PEPTIDE-SYNTHESIS, THYMOSIN BETA 4, GROWTH-HORMONE, COUNTERFEIT BEVACIZUMAB, PUBLIC-HEALTH, PHARMACEUTICAL-PREPARATIONS, INTRAVITREAL INJECTION, IDENTIFICATION, MEDICINES, QUALITY

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Citation

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MLA
Janvier, Steven, Karlien Cheyns, Michaël Canfyn, et al. “Impurity Profiling of the Most Frequently Encountered Falsified Polypeptide Drugs on the Belgian Market.” TALANTA 188 (2018): 795–807. Print.
APA
Janvier, S., Cheyns, K., Canfyn, M., Goscinny, S., De Spiegeleer, B., Vanhee, C., & Deconinck, E. (2018). Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market. TALANTA, 188, 795–807.
Chicago author-date
Janvier, Steven, Karlien Cheyns, Michaël Canfyn, Séverine Goscinny, Bart De Spiegeleer, Celine Vanhee, and Eric Deconinck. 2018. “Impurity Profiling of the Most Frequently Encountered Falsified Polypeptide Drugs on the Belgian Market.” Talanta 188: 795–807.
Chicago author-date (all authors)
Janvier, Steven, Karlien Cheyns, Michaël Canfyn, Séverine Goscinny, Bart De Spiegeleer, Celine Vanhee, and Eric Deconinck. 2018. “Impurity Profiling of the Most Frequently Encountered Falsified Polypeptide Drugs on the Belgian Market.” Talanta 188: 795–807.
Vancouver
1.
Janvier S, Cheyns K, Canfyn M, Goscinny S, De Spiegeleer B, Vanhee C, et al. Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market. TALANTA. 2018;188:795–807.
IEEE
[1]
S. Janvier et al., “Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market,” TALANTA, vol. 188, pp. 795–807, 2018.
@article{8575277,
  abstract     = {Advances in biotechnology and the chemical synthesis of peptides have made biopharmaceuticals and synthetic peptide drugs viable pharmaceutical compounds today and an important source for tomorrow's drugs and therapies. Unfortunately, also falsifications and counterfeit versions of these powerful and promising drugs are offered illegally via the intemet. Since these falsified preparations are produced outside the legally required quality systems, end-users have no guarantee regarding the efficacy and safety of these products. Although falsified samples of biotherapeutics were already analysed, looking at a specific aspect of their quality or identity, no systematic studies have been performed regarding the presence of different impurities or possible contaminations. Therefore, in order to obtain a better understanding of the potential health risks related to the usage of falsified polypeptide drugs we performed a systematic screening of the ten most frequently encountered falsified peptide drugs on the Belgian market acquired from three different suspected illegal internet pharmacies. The screening incorporated the analysis of the active pharmaceutical ingredient (API), API-related impurities, small molecule contaminants (defined as organic small molecules not belonging to the other categories), elemental impurities and residual solvents. This comprehensive study showed that these type of falsified drugs not only have a high variation in amount of drugs per unit and a low purity (ranging between 5% and 75% for cysteine containing peptides), but also contained the known toxic class one elemental impurities arsenic (As) and lead (Pb). One sample was contaminated with Pb while multiple samples were found with concentrations up to ten times the ICH toxicity limit for parenteral drugs. Subsequent speciation of As confirmed the elevated concentrations for As and demonstrated that all As was present in the more toxic inorganic form. Together with the (sometimes) high amount of peptide impurities and the inherent dangers associated with the use of unauthorized peptide drugs (such as doping peptides or preclinical drugs) this study confirms the reported potential health risks patients/users take when resorting to falsified peptide drugs. Moreover, the presence of the carcinogen As and the known accumulation in human tissues of Pb raises questions about potential sub-acute to chronic toxicity due to the long term administration of these falsified peptide drugs.},
  author       = {Janvier, Steven and Cheyns, Karlien and Canfyn, Michaël and Goscinny, Séverine and De Spiegeleer, Bart and Vanhee, Celine and Deconinck, Eric},
  issn         = {0039-9140},
  journal      = {TALANTA},
  keywords     = {Falsified medicines,Peptide drugs,Heavy metals,Impurity profiling,Mass spectrometry,PHASE PEPTIDE-SYNTHESIS,THYMOSIN BETA 4,GROWTH-HORMONE,COUNTERFEIT BEVACIZUMAB,PUBLIC-HEALTH,PHARMACEUTICAL-PREPARATIONS,INTRAVITREAL INJECTION,IDENTIFICATION,MEDICINES,QUALITY},
  language     = {eng},
  pages        = {795--807},
  title        = {Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market},
  url          = {http://dx.doi.org/10.1016/j.talanta.2018.06.023},
  volume       = {188},
  year         = {2018},
}

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