Multiwavelength spectrophotometric determination of acid dissociation constants

Part II. First derivative vs. target factor analysis

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Purpose. Acid dissociation constants (pK(a) 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 pK(a) values, making precise pK(a) determination difficult using conventional spectrophotometric titration. In this work, we investigate a multiwavelength spectrophotometric titration (WApH) method for the determination of pK(a) 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 KCl solution at 25 ± 0.5°C. Mathematical treatments based on the first derivative spectrophotometry procedure and the target factor analysis method were applied to calculate the pK(a) values from the multiwavelength absorption titration data. Results. pK(a) 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 pK(a) 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 pK(a) 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 pK(a) values or with closely overlapping pK(a) 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.

Original languageEnglish
Pages (from-to)374-381
Number of pages8
JournalPharmaceutical Research
Volume16
Issue number3
Publication statusPublished - 1999

Fingerprint

Factor analysis
Titration
Statistical Factor Analysis
Ionization
Phenolphthalein
Derivatives
Acids
Anions
Aminosalicylic Acid
Biological membranes
Molecules
Benzoic Acid
Niacin
Spectrophotometry
Phenol
Optical systems
Pharmaceutical Preparations
Water
Optical Devices
Experiments

Keywords

  • Acid dissociation constants
  • Fibre optics
  • First derivative spectrophotometry
  • Multiwavelength spectrophotometric titration
  • pK(a)
  • Target factor analysis

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

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title = "Multiwavelength spectrophotometric determination of acid dissociation constants: Part II. First derivative vs. target factor analysis",
abstract = "Purpose. Acid dissociation constants (pK(a) 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 pK(a) values, making precise pK(a) determination difficult using conventional spectrophotometric titration. In this work, we investigate a multiwavelength spectrophotometric titration (WApH) method for the determination of pK(a) 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 KCl solution at 25 ± 0.5°C. Mathematical treatments based on the first derivative spectrophotometry procedure and the target factor analysis method were applied to calculate the pK(a) values from the multiwavelength absorption titration data. Results. pK(a) 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 pK(a) 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 pK(a) 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 pK(a) values or with closely overlapping pK(a) 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.",
keywords = "Acid dissociation constants, Fibre optics, First derivative spectrophotometry, Multiwavelength spectrophotometric titration, pK(a), Target factor analysis",
author = "Tam, {K. Y.} and K. Tak{\'a}cs-Nov{\'a}k",
year = "1999",
language = "English",
volume = "16",
pages = "374--381",
journal = "Pharmaceutical Research",
issn = "0724-8741",
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TY - JOUR

T1 - Multiwavelength spectrophotometric determination of acid dissociation constants

T2 - Part II. First derivative vs. target factor analysis

AU - Tam, K. Y.

AU - Takács-Novák, K.

PY - 1999

Y1 - 1999

N2 - Purpose. Acid dissociation constants (pK(a) 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 pK(a) values, making precise pK(a) determination difficult using conventional spectrophotometric titration. In this work, we investigate a multiwavelength spectrophotometric titration (WApH) method for the determination of pK(a) 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 KCl solution at 25 ± 0.5°C. Mathematical treatments based on the first derivative spectrophotometry procedure and the target factor analysis method were applied to calculate the pK(a) values from the multiwavelength absorption titration data. Results. pK(a) 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 pK(a) 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 pK(a) 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 pK(a) values or with closely overlapping pK(a) 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.

AB - Purpose. Acid dissociation constants (pK(a) 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 pK(a) values, making precise pK(a) determination difficult using conventional spectrophotometric titration. In this work, we investigate a multiwavelength spectrophotometric titration (WApH) method for the determination of pK(a) 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 KCl solution at 25 ± 0.5°C. Mathematical treatments based on the first derivative spectrophotometry procedure and the target factor analysis method were applied to calculate the pK(a) values from the multiwavelength absorption titration data. Results. pK(a) 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 pK(a) 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 pK(a) 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 pK(a) values or with closely overlapping pK(a) 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.

KW - Acid dissociation constants

KW - Fibre optics

KW - First derivative spectrophotometry

KW - Multiwavelength spectrophotometric titration

KW - pK(a)

KW - Target factor analysis

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