Theory and practice of pharmacopoeial control of quality of drugs and excipients VIII. End-point indication and other conditions for the titration of primary aromatic amines in the European Pharmacopoeia (Ph. Eur.)

Authors: Jan Šubert ;  Jozef Kolář
Published in: Čes. slov. Farm., 2019; 68, 34-36
Category: Short Article


Indication of the equivalence point for the titration of primary aromatic amines (sulphonamides, etc.) with sodium nitrite solution according to Ph. Eur. (2.5.8) is performed electrometrically or using a prescribed indicator, the electrometric method not being specified. Better reproducibility of the assay results would add to Ph. Eur. the electrometric method to be used for the indication and suitable electrodes for it. The authors of the paper propose a potentiometric indication, which is in Ph. Eur. widely used. Further, they propose to consider whether in Article 2.5.8. Ph. Eur. indications using an indicator as an alternative to the instrumental indication required. The titration in the presence of hydrochloric acid favourably affects the addition of potassium bromide, cooling the solution prior to the titration prescribed by Ph. Eur. is not needed.


Ph. Eur. – titration of aromatic amines with sodium nitrite – endpoint indication – other conditions


1. European Pharmacopoeia Online 9.5 ( Accessed 26-11-2018)

2. Connors K. A. Reaction Mechanisms in Organic Analytical Chemistry. New York: John Wiley 1973; 236–238.

3. Symboly veličin a názvosloví používané v analytické chemii. Praha: Academia 1973; 40.

4. Daas A. G. J., Miller J. H. McB. Content limits in the European Pharmacopoeia. Part 1. Pharmeuropa 1997; 9, 148–156.

5. Coenegracht P. M. J., Franke J. P., Metting, H. J. The automatic amperometric and potentiometric microtitration of pharmaceutically important sulfanilamide derivatives by diazotization with nitrite. Anal. Chim. Acta 1973; 65, 375–384.

6. Surmann P. Quantitative Analyse von Arzneistoffen und Arzneizubereitungen. Stuttgart: Wissenschaftliche Verlagsgesellschaft 1987; 51.

7. Kucharský J., Erben J., Mikule V. Elektrometrická titrace sulfonamidů. Českoslov. Farm. 1954; 3, 284–285.

8. Ueno K., Tachikawa T. Potentiometric titration of sulfanylamide with sodium nitrite. Japan Analyst 1962; 11, 554–558.

9. Larocca J. P., Waters, K. L. The potentiometric titration of the sulfa drugs. J. Am. Pharm. Assoc. Sci. Ed. 1950; 39, 521–523.

10. Šubert J. Příspěvky k analytice léčiv. VI. Studium podmínek pro diazotační titrace léčiv za potenciometrické indikace a standardizaci odměrného dusitanu sodného. Farm. Obzor 1981; 50, 273–278.

11. Metrohm AG, Herisau. Automatic potentiometric titration of sulfanilamide. Titration Application Note T-157 ( 8.12.2018).

12. Český lékopis 1997 – Doplněk 1999, 2. díl. Praha: Grada Publishing 1999; 5004–5005.

13. Český farmaceutický kodex. 1. vydání (ČFK 1). Praha: X-EGEM 1993.

14. Matrka M., Kroupa J. Analyse von Farbstoffen und von bei der Farbstofferzeugung anfallenden Zwischenprodukten X. Potentiometrische Titrationen mit einer Nitritmasslösung unter Verwendung bimetallischer Elektrodensysteme. Collection Czech. Chem. Commun. 1970; 35, 995–1000.

15. Matrka M., Pípalová J. K problematice potenciometrických titrací aromatických aminů dusitanem. Chem. Prům. 1973; 23, 149–152.

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