Identification of Pharmaceutical Impurities in Formulated Dosage Forms

Pan, Changkang; Liu, Frances; Motto, Michael G.

doi:10.1002/jps.22376

Cited by 51 publications

(39 citation statements)

References 117 publications

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“…Again, this converts to a Schiff base, which cyclizes and isomerizes as illustrated in Figure 13. This reaction is usually observed for Lys that reacts the most rapidly with reducing sugars, but also for Arg, Asn and Gln [67,91,99]. β-elimination of disulfide bonds leads to free thiol groups.…”

Section: Apis (Drug Substances)mentioning

confidence: 99%

“…Eur. include normal-phase HPLC, thin layer chromatography (TLC) and capillary zone electrophoresis (CZE), while other detection techniques may consist of NMR, fluorescence, refractive index and evaporative light scattering [66,67].…”

Section: Purity Of Peptidesmentioning

confidence: 99%

“…Although highly pure solvents (HPLC grade) are used, they may still contain some impurities at low levels, inducing unwanted reactions [67]. In Figure 10, some typical examples of impurities observed in synthesized peptides are presented.…”

Section: Purity Of Peptidesmentioning

confidence: 99%

“…For example, among the amino acids, Asn and Asp are the most unstable residues [90].The major chemical degradation reactions are: deamidation, hydrolysis, peptide bond cleavage, oxidation, Maillard reaction, β-elimination, enantiomerization, isomerization and dimerization [67,[90][91][92]. Next to stability issues of the peptide APIs or drug substance, formulated finished drug products (FDPs) show also degradation.…”

Section: Degradation Of Peptidesmentioning

confidence: 99%

“…Generally, a dry formulation is more stable than an aqueous formulation. However, these excipients or impurities that are present in the excipients may also react with the peptides, inducing degradation [67,91,93,94]. Thus, it is crucial to select the most appropriate excipient [95,96].…”

Section: Degradation Of Peptidesmentioning

confidence: 99%

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Purity profiling of Peptide Drugs

Verbeken¹

2012

JBABM

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The quality of a peptide drug mainly depends on its impurity profile, with the emphasis on the related impurities. These impurities may be biomedically active, alter the desired efficacy or induce unwanted toxicity, an aspect which is termed the "functional quality" of the peptide drug. Therefore, regulatory authorities have set up guidances or have legally established specification limits to assure a consistent purity of these peptide drugs. For the active pharmaceutical ingredients (APIs), the pharmacopoeial monographs are legally binding. Additional information can be found in regional and international guidelines. For the finished pharmaceutical drug products (FDPs) containing peptide active ingredients, only general guidelines are available. The construction of a complete related-impurity profile is very challenging due to the wide availability of different protecting groups, coupling agents and additives that may be used during peptide synthesis. In addition, chemical degradation, occurring during synthesis, formulation or at storage, may occur as well, including not only so-called pure chemical degradation but interaction with excipients as well. This review provides an update of the regulatory and scientific rationales behind the related impurities in peptide drugs.

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Section: Apis (Drug Substances)mentioning

confidence: 99%

Section: Purity Of Peptidesmentioning

confidence: 99%

Section: Purity Of Peptidesmentioning

confidence: 99%