Science

pKa Validations

When Sirius was founded in 1990, no instrument was available for determining pKa values from potentiometric titration curves or pH-UV data. Although the classical techniques were understood, the measurement of pKa values of drugs was a highly specialised task. We introduced software and dedicated instrumentation that could handle small quantities of sample, and cosolvent methods for poorly soluble samples.
A large number of pharmaceutical companies, universities and agrochemical companies now use our instruments, and we believe we provide the de facto worldwide standard for pKa measurement.

Sirius instruments measure pKa values by potentiometric titration and spectrophotometric titration. These  classical techniques have been used for many years for pKa measurement. They were outlined in OECD Guideline 112 for the measurement of Dissociation Constants (pKa values) in Water which was adopted in 1981, and described in a widely-accepted monograph (Albert, A.; Serjeant, E. P., The Determination of Ionisation constants. Chapman and Hall, London, 2nd Edition 1984) that we used during development of our technology.

Sirius-measured pKa values feature in many publications, some of which are listed in our bibliography. Of these, the following were validation studies that compared our pKa results with independently-measured pKa values:

20 compounds compared: J. Comer, K. Chamberlain and A. Evans. Validation of pH-metric technique for measurement of pKa and logPow of ionizable herbicides. SAR QSAR Environ. Res., 1995, 3, 307-313

25 compounds compared: K. Takács-Novák, K. J. Box and A. Avdeef. Potentiometric pK(a) determination of water-insoluble compounds: Validation study in methanol/water mixtures. Int. J. Pharm., 1997, 151, 2, 235-248 25 compounds compared: K. Y. Tam and K. Takács-Novák. Multiwavelength Spectrophotometric Determination of Acid Dissociation Constants: A Validation Study. Anal. Chim. Acta, 2001, 434, 157-167

71 compounds compared: K. Box, C. Bevan, J. Comer, A. Hill, R. Allen and D. Reynolds. High-throughput measurement of pKa values in a mixed-buffer linear pH gradient system. Anal Chem, 2003, 75, 4, 883-92

 

The graph compares 32 pKa values measured on SiriusT3 with published measured pKa values.