Solubility Across a pH Range

Following Beer s law given in Equation 6.1, for a given wavelength, equivalent concentrations of species with a different molar extinction coefficient will not have an equivalent absorbance. Under these circumstances, the use of calibration curves determined from compounds dissolved in organic solvents and therefore present only in the neutral form will not be appropriate for the determination of the concentration of a species that is ionized. 

This problem can be overcome by determining a scan of the samples across a range of wavelengths, typically 200-400 nm and selecting the wavelength at which the extinction coefficient is equivalent for all species, the isosbestic point (DMSO absorbance will cause interference if scanning is done at wavelengths much lower than 230 nm), to plot the calibration curves and thus calculate the concentration of the analyte present. 

Another major benefit to medicinal chemists of providing pH profile data is the early identification of stability issues - if the solubility and calibration spectra do not match, it will indicate that degradation of the compound may be occurring. 

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