Handbook of Solvents - George Wypych - ChemTech - Ventech!

14.21.1 Use of solvents in manufacture of drugs 981
14.21.1.2.1.5 Solvents used for extraction and preparative chromatography
As in the precedent cases they have to be absolutely inert (as far as it is possible) and with a
high degree of purity for the reasons already evoked. In case of preparative chromatography
a special care will be taken concerning the chemical inertia to adsorbate 9 of the solvents
constituting the mobile phase and the fact that impurities or additives contained in the solvents
in a way not under control could impair significantly the reproducibility of the retention
times.
14.21.1.2.1.6 Nature and origin of impurities contained in solvents 10
It should be reminded here that a solvent used at the industrial level is rarely pure (we mean
here no impurity analytically detectable).
Industrial solvents may contain:
• impurities coming from their origin or their manufacturing process
• impurities originating from the container during transportation
• stabilizers
• denaturing agents
• impurities resulting from a transformation of the solvent during the chemical
reaction
These impurities or side products should be look for as far as it is possible when assessing
the purity of the solvent. In fact they could be less volatile than the main solvent and
could finally concentrate in the pharmaceutical product.
We will now review shortly the nature of all these kinds of impurities of the most often
used solvents.
14.21.1.2.1.6.1 Impurities coming from the origin or the manufacturing process of the
solvent 1,10
Table 14.21.1.2. Solvent impurities
Class of solvents Possible impurities (according to the manufacturing process)
Hydrocarbons
Toluene Methylthiophene, benzene, paraffinic hydrocarbons
Xylene
Mixture of ortho, meta and para isomers, paraffinic hydrocarbons,
ethyl benzene, sulfur compounds
Cyclohexane Benzene, paraffinic hydrocarbons, carbonyl compounds
Halogenated compounds
Dichloromethane Chloroform, carbon tetrachloride, chloromethane
Chloroform
Chlorine, carbonyl chloride (phosgene), dichloromethane, carbon
tetrachloride, hydrogen chloride
Carbon tetrachloride Chlorides, chlorine, carbon disulfide
Methanol
Alcohols
Water, acetone, formaldehyde, ethanol, methyl formate,
dimethylether, carbon dioxide, ammonia