1 4-Hydroxybenzoic acid 4.28 mg
2 Butyl-4-hydroxybenzoate 3.61 mg
3 Propyl-4-hydroxybenzoate 3.75 mg
4 Ethyl-4-hydroxybenzoate 4.54 mg
5 Methyl-4-hydroxybenzoate 4.22 mg
Inactive ingredient
Measuring cell: DSC820
Pan: Aluminum 40 µl, hermetically sealed
Sample preparation: Sample pressed down in the pan
DSC measurement:
1 Heating from 205 °C to 220 °C
2 Heating from 50 °C to 80 °C
3 Heating from 85 °C to 100 °C
4 Heating from 105 °C to 120 °C
5 Heating from 120 °C to 130 °C
Heating rate for all experiments was 1 K/min
Atmosphere: Air, stationary environment, no flow
The melting curves of the above mentioned substances are shown. The purity of the samples are evaluated using the DSC method for purity determination according to van't Hoff. As an example, the detailed evaluation for 4-hydroxybenzoic acid is described (see also application 40 on page 81).
Evaluation of the purity between 10% and 50% of the peak height using the baseline type ‘line’. In addition, the purity of the substances was determined with HPLC.
Substance | 1 4-Hydroxy-benzoic acid | 2 Butyl-ester | 3 Propyl-ester | 4 Ethyl-ester | 5 Methyl-ester |
---|---|---|---|---|---|
Melting point, °C | 214.30 | 69.10 | 96.43 | 115.79 | 125.75 |
Heat of fusion, J/g | 244.13 | 159.87 | 151.83 | 160.21 | 173.46 |
Purity DSC, mole % | 99.90 | 99.76 | 99.65 | 99.88 | 99.89 |
Purity HPLC, % | 100.0 | 99.96 | 99.94 | 99.87 | 99.98 |
The substances investigated show a very high degree of purity. The results from DSC and from HPLC can be regarded as identical within the limits of accuracy.
When comparing the results of the two methods, one must allow for the fact that the HPLC results are expressed in units of weight percent, and the DSC results in mole percent.
Purity using DSC and HPLC, 4-Hydroxybenzoic Acid and its Esters | Thermal Analysis Application No. HB837 | Application published in METTLER TOLEDO TA Application Handbook Pharmaceuticals