Multiwavelength spectrophotometric determination of acid dissociation constants of ionizable drugs

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 17; no. 4; pp. 699 - 712
• Main Authors: Allen, R.I., Box, K.J., Comer, J.E.A., Peake, C., Tam, K.Y.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.1998; Elsevier Science
• Subjects: Acid dissociation constants; Analysis; Biological and medical sciences; Fiber optics; General pharmacology; Hydrogen-Ion Concentration; Ions; Kinetics; Medical sciences; Multiwavelength spectrophotometric titration; p Ka; pH-metric titration; Pharmaceutical Preparations - chemistry; Pharmacology. Drug treatments; Spectrophotometry, Ultraviolet - methods; Target factor analysis; Multiwavelength spectrophotometric titration; pH-metric titration; p K a; Acid dissociation constants; Target factor analysis; Fiber optics; Antimalarial; Nitrazepam; Fenamic acid derivatives; Dissociation constant; Hypnotic; Pyridoxine; Photodiode; Quinine; Non steroidal antiinflammatory agent; pH metering; Niflumic acid; Detector; Acids; Ionization; Parasiticid; Benzodiazepine derivatives; Diode array; Sedative; pK; Spectrophotometry; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(98)00010-7

A multiwavelength spectrophotometric approach has been developed to determine acid dissociation constants (p K a values) of sparingly soluble drug compounds. UV absorption spectra of the drug solution are acquired using a versatile device based on a fiber optics dip probe, a light source and a photodiode array (PDA) detector while the pH and the ionic strength of the chemical system is manipulated precisely by means of a commercially available titrator. Target factor analysis (TFA) has been applied to deduce the p K a values from the multiwavelength UV absorption data recorded at different pH values. We have called this multiwavelength approach the WApH technique because the p K a results are determined from changes in Wavelength and Absorbance as a function of pH (WApH). The WApH technique is exemplified by using several pure drugs, namely, niflumic acid, nitrazepam, pyridoxine, quinine and terbutaline. The p K a values obtained agree well with those derived from pH-metric titrations. It has been demonstrated that the WApH technique is able to deduce p K a values with high accuracy even if the absorption spectra of the reacting species are very similar.