Residual solvents definition

ICH Q3A(R) has classified impurities as organic impurities, inorganic impurities, and residual solvents. This classification system provides a useful framework for the discussion of impurities and serves to create fixed and consistent definitions for impurities in pharmaceutical substances. 

Besides traces of residual solvent, the presence of three types of compounds was detected. In addition to unreacted ds-3-hexene (C6H12), the most important product was Ci0H22 or C10H20 which most likely was formed by f-butylation of c -3-hexene followed by rapid hydridation, Addition of f-Bu to ds-3-hexene produces a secondary carbenium ion which may rearrange to form a tertiary carbenium ion prior to hydridation. Significantly, the absence of C12H26 indicates the absence of ethylation and surest addition of r-Bu to 1,4-unsaturations followed by rapid termination by hydridation. Proton elimination might have also occurred but could not be definitively established. 

Of these molecular variants, one is the desired product with the desired properties with respect to biological activity and efficacy. Some structurally related variants (referred to as product related ) exhibit similar properties to the desired product and are therefore not considered as impurities. However, there may also be structurally related variants with altered properties with respect to biological activity, efficacy and/ or safety, which must be considered as impurities. In addition to the molecular variants of the protein (or protein-like) product, additional process-related substances may be part of a biotechnological drug substance, e.g., cell culture media, host cell proteins, DNA residuals, solvents, bacteria and/or viruses. This suggests that the determination of purity of these products (which is referred to as purity estimation rather than purity determination ) is a complex analytical issue. A purity estimation consists of both the definition of the heterogeneity of the protein (or proteinlike) product, and the identification and quantitation of product- and process-re-... 

As introduced in Sect. 8.2.1, the roadmap of any QbD approach starts with the Target Product Proflle (TPP) definition this summary of drug characteristics (e.g., pharmacokinetic properties and stability) will serve as the basis for a set of performance parameters (e.g., immediate release drug 80 % in < 30 min, 36-month shelf life at room temperature, respectively) that, in turn, will be linked to a set of Critical Quality Attributes (CQAs e.g., shelf life will depend on the amount of residual solvents due to its impact on chemical stability release profile will depend on particle size for some drugs due to its impact on dissolution). 

Here two components, the free phenol and the intact ester, are included in the residue definition. Usually, analytical methods for the determination of bromoxynil and its octanoate begin with hydrolysis during maceration of the sample. If those methods are validated, the sole fortification of the octanoate is sufficient. However, in other existing methods, hydrolysis follows a separate extraction step. In that case, the chosen solvent must be able to extract both compounds with equal efficiency. 

Often solvents do not extract 100% of the total radioactive residue. In this case, knowledge about the concentration of the target analyte(s) in the extract and the filter cake is necessary. Even if large amounts of radioactivity remain in the solid residual materials, the extraction efficiency may be sufficient if this unextracted radioactivity is permanently bound to the matrix or if it is associated with compounds which are not included in the residue definition. Finally, in all cases a well performed metabolism study can provide the answers needed, even where residues in the edible parts of treated crops or animals do not occur. If incurred residues do not occur, clearly the determination of extraction efficiency is not required. 

The classic definition of asphaltenes is based on the solution properties of petroleum residua in various solvents. The word asphaltene was coined in France by J.B. Boussingault in 1837. Boussingault described the constituents of some bitumens (asphalts) found at that time in eastern France and in Peru. He named the alcohol insoluble, essence of turpentine soluble solid obtained from the distillation residue "asphaltene", since it resembled the original asphalt. 

The potential for the preservation of lipids is relatively high since by definition they are hydrophobic and not susceptible to hydrolysis by water, unlike most amino acids and DNA. A wide range of fatty acids, sterols, acylglycerols, and wax esters have been identified in visible surface debris on pottery fragments or as residues absorbed into the permeable ceramic matrix. Isolation of lipids from these matrices is achieved by solvent extraction of powdered samples and analysis is often by the powerful and sensitive technique of combined gas chromatography-mass spectrometry (GC-MS see Section 8.4). This approach has been successfully used for the identification of ancient lipid residues, contributing to the study of artifact... 

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