Practical issues and potential interferences

In practice, instrument companies provide software to perform purity calculations, but there is still a lot of care needed in the method. First of aU it has to be noted that thermal gradients across a sample will affect the rate of melting and the resulting peak shape. For this reason sample sizes must be small, typically about 1 mg, and the scan rates slow, typically l°C/min. Even so the rate of transfer of heat to the sample, expressed as the thermal resistance constant Ro, will influence the rate of melt, and this varies from instrument to instrument and with pan type used. Rq must therefore be determined under the conditions of the test and used in the calculations. See Section 1.5.2 for a description of how this is measured. It is very important that this is done correctly whilst in one sense the method is not based on the 

If the trace looks to be acceptable then begin the purity determination by setting the limits for the partial integration. In some systems these may be fixed by the software or in others chosen by the operator. The early part of melt below 5% is unlikely to be useful, and limits are often set between 5 and 60% of the peak area which corresponds to the equilibrium melt region (leading edge of melt) for the majority of materials [40]. If the 60% limit falls on the tail of the peak, this is evidence of excessive energy under the tail, which could be due to solid-liquid interactions which tend to result in an unduly symmetrical peak shape. 

In general results should be reproduced to give confidence, and as with all extrapolated data some variability can be expected. To some extent this will be operator dependent but typically should be to within a few tenths of a percent. The method may be optimised for a given substance with the general guideline that the purer the material, the slower the scan rate that should be used and that the more impure the material, the faster the scan rate that can be used (since peaks will be broader). We have found 0.5°C/min to give most accurate and reproducible data for very pure materials. 

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Practical issues and potential interferences Excipient compatibility... 

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