scholarly journals EXPLORING OF ACID-BASIC PROPERTIES, DEVELOPMENT AND VALIDATION OF THE METHOD OF QUANTITATIVE DETERMINATION OF ORIGINAL PHARMACEUTICAL SUBSTANCE

2019 ◽  
Vol 8 (1) ◽  
pp. 66-71
Author(s):  
G. M. Alekseeva ◽  
V. F. Apraksin ◽  
Yu. E. Generalova
Keyword(s):  
Quantitative Determination ◽  
Active Compound ◽  
Dissociation Constants ◽  
Acid Dissociation ◽  
Bromocresol Green ◽  
Acid Base ◽  
Indicator Method ◽  
Pharmaceutical Substance ◽  
Basic Properties

Introduction. The object of analysis was a newly synthesized organic substance, a derivative of 4-aminobenzoic acid and malonic ester  – 4,4’-(propandiamido) sodium dibenzoate, which has an antisteatotic effect. For the quantitative determination of pharmaceutical substances, it is preferable to use titrimetric methods of analysis, since they are absolute and allow us to estimate the content of the active compound in the substance without using standard samples. Aim. The objective of this work was to develop and validate a quantitative determination method for 4.4’-(propandiamido) sodium dibenzoate. Materials and methods. The analyzed compound is a salt of a weak dibasic acid, which exhibits basic properties in an aqueous solution; therefore, for its quantitative determination, a direct acid-base titration method (acidimetry) was proposed. The method of quantitative determination of the active compound in the substance 4,4’-(propandiamido) sodium dibenzoate will be used in future studies for routine analysis, therefore a visual (indicator) method for determining the end point of the titration has been chosen. To prove the suitability of the developed method and the possibility of obtaining reliable results of the quantitative content of the active compound in the newly synthesized pharmaceutical substance the used analytical method was validated. Results and discussion. The study of the acid-base properties of the newly synthesized substance was carried out using the method of potentiometric titration, on the basis of which the values of the dissociation constants were calculated. Using spreadsheets, the pKa1 and pKa2 values were calculated using a titration model of a multi-basic acid, the pKa values of which are 7.2 and 5.0. The titration curve that was constructed from the experimental data and the curve constructed from the calculated values of the dissociation constants almost completely overlapped with each other. Based on the data obtained, a 0.1% water-alcohol solution of bromocresol green (blue) with pT=4.6 was selected for titration, the color transition interval of which falls into the titration jump of the analyte. The developed methodology was validated according to the requirements of the XIV edition State Pharmacopoeia of the Russian Federation by the following indicators: specificity, linearity, accuracy, precision (convergence and internal reproducibility), robustness, analytical domain. Conclusion. As a result of the performed studies, the values of acid dissociation constants of the newly synthesized pharmaceutical substance 4,4’-(propandiamido) sodium dibenzoate were determined, and a method for quantitative determination was developed and validated using acidbase titration.

Chromatographic Determination of Thermodynamic Acid Dissociation Constants of Tetracycline Antibiotics and Their Epimers

2019 ◽  
Vol 57 (8) ◽  
pp. 745-750
Author(s):  
İlkay Konçe ◽  
Ebru Çubuk Demiralay ◽  
Hülya Yılmaz Ortak
Keyword(s):  
Experimental Data ◽  
Dissociation Constant ◽  
Binary Mixtures ◽  
Dissociation Constants ◽  
Reversed Phase ◽  
Acid Dissociation ◽  
Acid Dissociation Constant ◽  
Chromatography Method ◽  
Ph Values

Abstract The presented study describes the development of reversed-phase liquid chromatography method using a core-shell particle column with a pentafluorophenyl stationary phase for the dissociation constant (pKa) determination of the tetracycline group antibiotics (tetracycline, oxytetracycline, chlortetracycline) and their epimers (4-epitetracycline, 4-epioxytetracycline, 4-epichlortetracycline). The pH values were measured in the acetonitrile (ACN)–water binary mixtures, used as mobile phases, instead of in water and take into account the effect of the activity coefficients. Thermodynamic acid dissociation constant (pKa1) values of studied antibiotics and their epimers were calculated using retention factor (k) at different mobile phase pH values in studied binary mixtures with ACN percentages of 20, 25, 30 and 35% (v/v). Experimental data were analyzed by using an Origin 7.0 program to fit experimental data to the nonlinear expression derived. From calculated pKa1 values, the aqueous pKa values of studied compounds were calculated by different approaches and these values were compared.

scholarly journals Acid dissociation constants of glycopeptides

1977 ◽  
Vol 163 (1) ◽  
pp. 31-38 ◽  
Author(s):  
B M Austen ◽  
R D Marshall
Keyword(s):  
Amino Acid ◽  
Dissociation Constants ◽  
Acid Dissociation ◽  
Hydroxyl Group ◽  
Amino Acid Residues ◽  
Acid Base ◽  
Titration Curves ◽  
Pka Value ◽  
Hen’S Egg ◽  
Additional Amino Acid

Glycopeptides containing mainly four amino acid residues in the sequence Asn-Leu-Thr-Ser, with small amounts of additional amino acid residues, were isolated from enzymic hydrolysates of hen's-egg albumin. Heterogeneity of the carbohydrate moiety was confirmed. Acid-base titrations showed that the alpha-amino group has a pKa value of 6.43 at 25 degrees C. The standard free engery and entropy changes associated with the ionization at 25 degrees C were 37.2kJ-mol-1 and -0.014kJ-mol-1- K-1 respectively. The complications arising in the interpretation of titration curves of the glycopeptides, which are heterogeneous with respect to the peptide chain, were considered and discussed in the light of the earlier suggestion that the titration curve of the glycopeptide might be interpreted as being due in part to a structure in which the hydroxyl group of the threonine residue is hydrogen-bonded to the beta-aspartamido oxygen atom [Neuberger & Marshall (1968) in Symposium on Foods - Carbohydrates and their Roles (Schultz, H.W., Cain, R.F. & Wrolstad, R.W., eds.), pp. 115-132, Avi Publishing Co., Westport, CT]. It is concluded that either the glycopeptides do not contain a hydrogen bond of that type, or, if they do, that it cannot be recognized by acid-base-titration studies.

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