Handbook of Solvents - George Wypych - ChemTech - Ventech!

14.21.1 Use of solvents in manufacture of drugs 991
Table 14.21.1.7. Example of monograph
applied to new solvent: Ethyl acetate
Specifications
Controls Standards
Characters Clear liquid, colorless
Identification
A - Infrared spectrum
or
B - Refractive index
or
C - Gas chromatography
Assay
Complies
1.370 to 1.373
Complies
Ethyl acetate (purity) Not less than 99.5%
Table 14.21.1.8. Example of monograph
applied to recycled solvent: Ethyl acetate
Specifications
Controls Standards
Characters Clear liquid, colorless
Identification
Gas chromatography Complies
14.21.1.4.2 Solvents used for the DP manufacture
There is no other choice than to use the quality of solvents defined by a Pharmacopoeia. It is
true that there are still discrepancies between the pharmacopoeias of different countries. It is
hoped that the ICH process dealing with the harmonization of quality, safety and efficacy
amongst three main zones of the world (EU, USA, Japan) will progressively reduce the remaining
differences in dossiers submitted to Regulatory Authorities and the way the data
are evaluated.
As examples, Tables 14.21.1.10, 14.21.1.11, and 14.21.1.12 summarize specifications
for acetone, ethanol and isopropanol given by the Ph. Eur. and USP. As can be seen only the
Ph. Eur. monograph makes reference to volatile impurities to be tested for by GC.
14.21.1.5 Quality of solvents and analysis
The solvents, including water, are used in almost every area of analytical sciences: spectroscopy,
chromatography, potentiometry, electrochemistry. They should be characterized by a
set of properties making them suitable for use for their intended purpose.
14.21.1.5.1 Quality of solvents used in spectroscopy
As a general requirement, the solvents used in spectroscopy should be transparent and stable
towards the relevant range of wavelengths. They should be able to dissolve the substance
to be examined and not contain impurities affecting the stability of the substance or
the validity of the method (selectivity, repeatability, limit of detection, analytical response).
Theoretically the solvent chosen should have minimal interaction with the solute. But what
could be seen as a disadvantage could also be an important source of structural information.
What is called the solvent effect can help in UV, IR and NMR spectroscopies 34 e.g. in struc-
Tests
Water content
Related substances
Methanol
Ethanol
Ethyl chloride
Others impurities (sum)
Assay
Not more than 2.0%
Not more than 1.0%
Not more than 2.0%
Not more than 2.0%
Not more than 2.0%
Ethyl acetate (purity) Not less than 99.5%