S.G. Abdullina - Ph.D. (Pharm.), Associate Professor, Department of Pharmaceutical Chemistry with courses of Analytical and Toxicological Chemistry, Kazan State Medical University. E-mail: s.abdullina@mail.ru
E.A. Kalinkina - Aspirant, Department of Pharmaceutical Chemistry with courses of Analytical and Toxicological Chemistry, Kazan State Medical University. E-mail: kalinkina.ea@gmail.com

Erythromycin belongs to a group of bacteriostatic antibiotics. It was used to treat various infections. Water content is one of the qualitative characteristic of the pharmaceutical substance of Erythromycin. It should contains not more than 6,5 % of water according to the Russian and the European Pharmacopoeia and not more than 10,0 % according to the U.S. Pharmacopeia. Galvanostatic coulometry is a promising method for the determination of water. The purposes of the research are to develop and validate of method coulometric water determination by Karl Fischer titration for the pharmaceutical substance of Erythromycin. Validation of coulometric water determination was carried out measuring specificity, linearity and range, accuracy and precision. Water determination at three levels of erythromycin concentration in the test sample within the range of 70-130 % (meaning the acceptable level is 100 %) accounts for specificity of the proposed method. The relative standard deviation (RSD) is less than 1%. Linearity and range of the given method had been determined by statistical treatment of data for 9 samples with the addition of a known amount HYDRANAL®-Standard sodium tartrate dihydrate on 9 levels of concentration within the range from water concentration detected in the erythromycin (3,94 %) to 120 % of the rated water content of erythromycin (less than 6,5%). Relationship between quantity of electricity and water mass is linear and described by the equation: y=a+bx, where a=-0,380,26, b=11,090,18 (R=0,9991). Accuracy of the proposed method was evaluated by standart addition method and comparison with reference method. Determination of three concentration levels by 125 %, 150 % and 175 % of the identified water content of erythromycins was carried out. The ratio of found water content in the confidence interval of 97,5-102,5 % is included. This indicated that the above method is valid in accuracy. Evaluation of accuracy in comparison with the reference method which is volumetric Karl Fischer titration was performed on the results of six determinations. The calculated values of Fisher's exact test and Student's t-test is less than the tabulated Fcalc=9,33Ftabl=10,97 (p=0,01) and tcalc=0,2954ttabl=3,17 (p=0,01, n=12).The experimental results are free of systematic error. Coulometric titration is valid in accuracy. Precision was evaluated by determining the repeatability of the proposed method on 6 determinations on the same level of concentration. Standard deviation (SD=0,0258), relative standard deviation (RSD=0,7 %) and confidence interval for the mean value (ΔXavarage=0,03) were obtained. Based on the results the proposed method was considered to be valid in precision.

1. Abdullina S.G., Lira O.A., Petrova I.K. Kulonometricheskoe opredelenie vody' v lekarstvenny'x preparatax // Farmacziya. 2011. № 5. S. 15-16.
2. Gosudarstvennaya farmakopeya SSSR XI izd. M.: Mediczina. 1987. Vy'p. 1. 336 s.
3. Gosudarstvennaya farmakopeya SSSR X izd. M.: Mediczina. 1968. 1080 s.
4. Petrov S.I., Zharikova O.A. Kontrol' pravil'nosti opredeleniya vody' v kulonometricheskoj akvametrii // Zavodskaya laboratoriya: Diagnostika materialov. 2005. T. 71. № 12. S. 3-6.
5. Prakticheskoe rukovodstvo po antiinfekczionnoj ximioterapii // pod red. L.S. Strachunskogo, Ju.B. Belousova, S.N. Kozlova. Smolensk: MAKMAX. 2007.
6. Rukovodstvo po validaczii metodik analiza lekarstvenny'x sredstv // pod red. N.V. Jurgelya, A.L. Mladenczeva, A.V. Burdejna, M.A. Get'mana. M. 2007. 58 s.
7. Rukovodstvo ICH «Validacziya analiticheskix metodik. Soderzhanie i metodologiya» Q2(R1). Mezhdunarodnaya konferencziya po garmonizaczii texnicheskix trebovanij k registraczii mediczinskix lekarstvenny'x sredstv // Farmacziya. 2008. № 4. S. 3-10.
8. European Pharmacopoeia 7th ed. Monograph Erythromycin. 2011.
9. Fisher K. Neues Verfahren zur massanalytischen Bestimmungen des Wassergehaltes von Flussigkeiten und festen Körpern // Angew. Chem. 1935. V. 48. P. 394-396.
10. Scholz E. Karl-Fischer-Titration: Methoden zur Wasserbestimmung. Berlin: Shringer-Verlag. 1984. 133 p.
11. The United States Pharmacopoeia 36th ed. Monograph Erythromycin. 2013.