Download Click here to start the Download

DSC
Purity Determination
of Drug Substances
Drug substances have to be checked for purity as they are mostly used at
purity levels greater than 99.9%. The check is frequently performed by
HPLC although a further method is often necessary where High Performance Liquid Chromatography (HPLC) analysis is not suitable. In such
cases, the DSC 1 differential scanning calorimeter offers a reliable alternative.
Purity determination is performed by analyzing the melting behavior of the substance in question. The method is based
on van’t Hoff’s law of melting point depression.
The drug substance is slowly heated
and the DSC curve recorded. Peak shape
analysis of the main melting peak is performed semi-automatically with STARe
software. The evaluation of typical measurements is shown in Figure 1. Pure
p-hydroxybenzoic acid and various esters were heated to melting
point in hermetically sealed aluminum crucibles. Figure 1. below
shows the detailed evaluation of the
p-hydroxybenzoic acid.
The curve was evaluated between 10 and
50% peak height using the ‘line’ baseline
type. The purity of substances was also determined by HPLC. The results are summarized in Table 1.
The substances investigated show a high
degree of purity. The results from DSC and
from HPLC can be looked upon as being
identical within the limits of measurement accuracy.
e
STAR
} www.mt.com/dsc
Figure 1: Purity determination of 4-hydroxybenzoic acid and its butyl (2), propyl (3), ethyl (4) and methyl (5) esters.
Substance
1
Melting point
Enthalpy of fusion
214.3
244
100
Purity by DSC
Purity by HPLC
99.90
2
125.8
173
3
115.8
160
4
96.4
152
5
69.1
160
Unit
°C
J/g
99.89
99.88
99.65
99.76
mol%
99.96
99.94
99.87
99.98
wt%
Table 1: Purity of (1) 4-hydroxybenzoic acid, and the (2) butyl-, (3) propyl-, (4) ethyl- and (5) methyl-4-hydroxybenzoates.
METTLER TOLEDO
PharmaNews 7