OptiMelt Automated Melting Point System - Stanford Research ...

Appendix A Pharmacopeia vs. Thermodynamic Melting Points 812( MPpharma− MPthermo⎡ α ⎤∆ Hf=⎢⋅⎣2r⎥) (eqn. 5)⎦which can be rearranged to provide an equation for the thermodynamic correction:1/2⎡2∆Hf⎤ 1/2∆ T() r = MPpharma− MPthermo=⎢ ⎥r = ( ThermoCF) ⋅ r (eqn. 6)⎣ α ⎦According to eqn. 6 the thermodynamic correction is directly proportional to the squareroot of the ramping rate, and in order to calculate the thermodynamic meltingtemperature, it is necessary to know the value of the Thermodynamic Correction Factor,ThermoCF, for the melting point apparatus:( ThermoCF) r = MP −( ThermoCF rMPthermo = MPpharma−clearpoint) (eqn. 7)The above theory indicates that the value of the thermodynamic correction factor,ThermoCF, depends, among other things, on the (1) heat of fusion of the sample, (2) thethermal conductivity of the sample, (3) the thermal conductivity of the glass capillary,(4) the sample preparation/packing method, (5) sample size and (6) the geometry andconstruction of the oven. In practice, the value of ThermoCF is both compound andinstrument dependent and must be calculated through empirical determination.Since the same factors that affect the ThermoCF also affect the clear point, this derivationalso confirms that calibration of the temperature offsets requires carefully reproducingthe sample preparation procedures used during routine analysis.Thermodynamic Correction with OptiMeltA user programmable Thermodynamic Correction Factor, ThermoCF, can beprogrammed into the OptiMelt and used by the instrument to automatically calculateThermodynamic Corrections, ∆T(r)= (ThermoCF) r 1/2 , at the end of a melting pointdetermination.Tips• Thermodynamic corrections are appended to melting point Reports if Thermo MP isset to Calculate in the Options menu of the Melt Screen.• Use the ThermoCF menu button, in the Options Menu of the Melt Screen, to programthe value of ThermoCF for the compound being measured.• Compound specific thermodynamic correction factors can be stored within theanalysis methods saved to memory.• Use the Thermodynamic Corrections calculated by your OptiMelt to correct “rampdependent”clear points (manual or automatic) and to obtain a true thermodynamicmelting point for your samples – independent of the rate of heat rise used.• Empirical measurements have shown that in most cases a good approximation to theThermodynamic Correction Factor, ThermoCF, for the OptiMelt is a value of ~1.0,when r is expressed in standard units of [°C/min].OptiMelt Automated Melting Point System