Log P and pKa determination

Log D and pKa determinations:

Bioneer:FARMA determines LogD and pKa by the GLpKa-meter or HPLC methods.

GLpKa-meter
pKa and LogD is determined by potentiometric titration using a GLpKa-meter

pKa determination

Aqueous pH-metric pKa(s) are determined. The standard titration range is from pH 3 to 11. Sample must contain one or more group which ionises within the titration range.

Cosolvent assays can be performed for samples with a solubility of <0.25mM. Aqueous pKa values are then derived using a Yasuda-Shedlovsky extrapolation.

LogD determination

Octan-1-ol is used as standard partition solvent. Sample must contain at least one pKa value. Samples are measured in up to three different ratios of octanol to water, to assess both neutral and ion-pair partitioning Log D values.
LogP values between 1 and 5 are reported as standard.
Extrapolated logD vs. pH profile also provided.

Sample requirement: 10-15 mg of compound in powder form

HPLC method:
Apparent LogD and pKa values of poorly soluble compounds are determined by HPLC

HPLC retention times of the compound using mobile phases with specific pH values are determined. Based on the retention times logD is calculated for each pH value. A plot of logD vs pH will give apparent values for logD at relevant pH values.
This method also immediately determines the pKa value for an ionisable compound with a pKa value between 3 and 7. Although apparent pKa values are obtained they are typically in the range of + 0.5 units from experimentally determined pKa values.
Because of the very low variability in the determinations, this procedure is very well suited for comparing small series of drug candidates, with inherent medium to low solubility in aqueous media and for correlations to absorption and distributions data from in-vitro and in-vivo studies.

Sample requirement: 1-2 mg in powder form, or 0.1 mL of a 10 mM stock solution in DMSO.