Chemistry Reference
In-Depth Information
proper functioning of the system used for the analyses (2, 4, 5). For example, the
stability of a stock reference standard solution is typically evaluated (duplicate injec-
tions) at time 0, 3, and 7 days following storage at both room temperature and refrig-
eration by preparing a fresh dilution at the target concentration level from the stored
stock standard and assaying it against freshly prepared system suitability standards
prepared from a freshly prepared stock solution. Sample solution stability is evalu-
ated in the same way (duplicate injections) at time 0, 3, and 7 days following storage
at both room temperature and refrigerated conditions by assaying a stored sample
against freshly prepared system suitability standards.
7.2.1 c
lASSIfIcAtIon
of
I
mPurItIeS
Active pharmaceutical ingredient (API) batches comprise a number of various sub-
stances. For chemically manufactured APIs, the major component is the API itself;
however, if the API is a salt, the counterion will also comprise a significant portion
of the batch. Other substances (impurities) from various sources are also commonly
present at different levels as listed in Table 7.2. The ICH guidance on Impurities in
Drugs Substances was accepted by the FDA in 2000 and provides a comprehensive
view of what sorts of impurities to expect, how to test for them (in general), how
to list them in specifications, and how to qualify their biological safety [6]. These
impurities can be organic, inorganic, or solvent related. The nature of the API and
the impurities present influence the choice of analytical procedures used in the quan-
tification of impurity levels.
tAble 7.2
classification of Impurities
Impurity type
examples
typical origin
• Organic
• Starting materials
• By-products
• Intermediates
• Degradants
• Reagents
• Ligands
• Chemical process
• Degradants may come from API
• Inorganic
• Reagents
• Ligands
• Catalysts
• Residual metals
• Inorganic salts
• Filter aids
• Chemical process
• Processing equipment
• Processing aids (i.e., ilter aids)
• Solvents
• Reaction solvents
• API isolation solvents
• Chromatographic solvents
• Chemical reaction
• Crystallization
• Precipitation
• Extraction or partition
• Chromatographic puriication
