title: Multiwavelength spectrophotometric determination of acid dissociation constants: Part II. First derivative vs. target factor analysis.
abstract: OBJECTIVE
  Acid dissociation constants (pKa values) denote the extent of ionization of drug molecules at different pH values, which is important in understanding their penetration through biological membranes and their interaction with the receptors. However, many drug molecules are sparingly soluble in water or contain ionization centres with overlapping pKa values, making precise pKa determination difficult using conventional spectrophotometric titration. In this work, we investigate a multiwavelength spectrophotometric titration (WApH) method for the determination of pKa values.
  
  
  METHODS
  Spectral changes which arise during pH-metric titrations of substances with concentration of about 10(-5) M were captured by means of an optical system developed in this study. All experiments were carried out in 0.15 M KCI solution at 25 +/- 0.5 degrees C. Mathematical treatments based on the first derivative spectrophotometry procedure and the target factor analysis method were applied to calculate the pKa values from the multiwavelength absorption titration data.
  
  
  RESULTS
  pKa values were determined by the WApH technique for six ionizable substances, namely, benzoic acid, phenol, phthalic acid, nicotinic acid, p-aminosalicylic acid and phenolphthalein.
  
  
  CONCLUSIONS
  The pKa values measured using the WApH technique are in excellent agreement with those measured pH-metrically. We have demonstrated that the first derivative spectrophometry procedure provides a relatively simple way to visualize the pKa values which are consistent with those determined using the target factor analysis method. However, for ionization systems with insufficient spectral data obtained around the sought pKa values or with closely overlapping pKa values, the target factor analysis method outperforms the first derivative procedure in terms of obtaining the results. Using the target factor analysis method, it has been shown that the two-step ionization of phenolphthalein involves a colorless anion intermediate and a red colored di-anion.
authors.affiliation: Sirius Analytical Instruments Ltd., East Sussex, United Kingdom.
authors.forename: K Y
authors.initials: KY
authors.lastname: Tam
authors.forename: K
authors.initials: K
authors.lastname: Takács-Novák
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry; D002400:Cathartics / Q000737:chemistry; D004355:Drug Stability; D005163:Factor Analysis, Statistical; D006863:Hydrogen-Ion Concentration; D009525:Niacin / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D020113:Phenolphthalein / Q000737:chemistry; D010795:Phthalic Acids / Q000737:chemistry; D013053:Spectrophotometry / Q000379:methods*
chemical_list: D002400:Cathartics; D004364:Pharmaceutical Preparations; D010795:Phthalic Acids; D009525:Niacin; C032279:phthalic acid; D020113:Phenolphthalein; D019817:Benzoic Acid