Determination of the pKa values of sparingly soluble substances in water revisited: application to some benzodiazepines
✍ Scribed by Baltazar de Castro; Paula Gameiro; José L.F.C. Lima
- Publisher
- Elsevier Science
- Year
- 1993
- Tongue
- English
- Weight
- 868 KB
- Volume
- 281
- Category
- Article
- ISSN
- 0003-2670
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✦ Synopsis
The acid-base behaviour of four benzodiazepines sparingly soluble in water (diazepam, medazepam, chlordiazepoxide and prazepam) was studied by potentiometric and spectrophotometric titrimetry in water. A method was devised to obtain the pK, values of these substances by potentiometric titrimetry in water-rich water-methanol media [up to 50% (v/v) methanol] by extrapolation to pure water, thus obviating the solubility problems associated with them. The method was found to be accurate and easily applicable, and the results obtained for the pK, values are identical, within experimental error, with those obtained in water. The operational criteria for applying this methodology are indicated.