Handbook of Solvents - George Wypych - ChemTech - Ventech!

990 Michel Bauer, Christine Barthélémy
14.21.1.4 Setting specifications for solvents
14.21.1.4.1 Solvents used for the raw material manufacture
For the raw materials we should distinguish between solvents:
• used during the synthesis
• and those used for the last step of the manufacture corresponding very often to the
crystallization process.
As a rule of thumb, the specifications set
Table 14.21.1.5. Examples of for solvents used for the crystallization step will
monographs
be more stringent than those used during the
synthesis.
Solvents used during the synthesis (of well For the intermediates of synthesis, if the
controlled origin)
origin of the solvent is under control (e.g., exis-
Character/Appearance
tence of contracts/Quality Assurance audits) a
20
Identification (IR, GC or n D )
simplified monograph is completely adequate
Purity GC (generally not less than 98%) (see Table 14.21.1.5) as long as the supplier provides
a detailed certificate of analysis where impurities
(including solvents) are properly
Table 14.21.1.6. Examples of
specified with acceptable limits. If the same sol-
monographs
vent is used for the crystallization step additional
purity tests are necessary (Table 14.21.1.6).
Final crystallization solvents (of well con-
For economic reasons, it may be necessary
trolled origin)
to recycle solvents. If so, the containers should
Character/Appearance
be fully identified in terms of storage:
20
Identification (IR, GC or n D ) • If solvents can be efficiently purified (e.g., by
Tests
redistillation) they must comply with the
Water content (0.1 to 0.5 depending on same specifications as those of fresh solvents
solvent type)
and consequently can be used in any
synthesis.
Residue on evaporation: not more than
0.01 per cent
• If they still contain volatile impurities
resulting from the reaction they come from,
Purity GC not less than 99 % (examine for
they can be recycled only for this reaction. In
denaturing agents and other potential impurities)
this case, the impurities should be identified
and their possible impact on the reaction
evaluated. In Tables 14.21.1.7 and 14.21.1.8
we have summarized possible specifications for a fresh batch of ethyl acetate used
for a defined chemical reaction and those for the recycled solvent.
We recommend working with reliable solvent suppliers who can give every assurance
on the quality of solvents provided to avoid any “unpleasant surprises”.
Water should be mentioned separately. If it is used during the synthesis of intermediates
the quality “drinking water” can be used without any problems. But if water is used during
the last step of the process, its quality must be in compliance with the requirements of
purified water as they are described in several pharmacopoeias. In Table 14.21.1.9 the requirements
for the Ph. Eur and USP are given as examples. Purified water is generally obtained
from the drinking water. It undergoes demineralization by either distillation or an
ion-exchange process. Particular attention has to be paid to microbiological quality.