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Russian Journal of Applied Chemistry, Vol. 75, No. 5, 2002, pp. 768!770. Translated from Zhurnal Prikladnoi Khimii, Vol. 75, No. 5,
2002, pp. 786!788.
Original Russian Text Copyright + 2002 by Illarionova, Abramova, Illarionov.
AND INDUSTRIAL ORGANIC CHEMISTRY
of Isoniconitic Acid Hydrazide Derivatives
E. A. Illarionova, L. V. Abramova, and A. I. Illarionov
Irkutsk State Medical University, Irkutsk, Russia
Irkutsk Institute of Railway Transport Engineers, Irkutsk, Russia
Received November 5, 2001
Abstract-A highly sensitive and selective procedure was developed for determining specific impurities of
isonicotinic acid hydrazide and vanillin in Metazid and Ftivazide preparations by thin-layer chromatography.
One of the principal characteristics of drugs is their
purity. In this work, we chose for our studies deriva-
tives of isonicotinic acid hydrazide, Metazid and
Ftivazide, which are widely used in medicine as anti-
In accordance with the preparation procedure, Met-
azid can contain as specific impurities isonicotinic
acid hydrazide (INAH) and formaldehyde. The initial
compounds for preparing Ftivazide are INAH and
vanillin whose content in the product should be moni-
tored. According to the existing regulations [1, 2], the
content of these specific impurities in Metazid and
Ftivazide should be determined chemically. Isonico-
tinic acid hydrazide is determined with iodine in the
presence of starch, and vanillin, by the reaction with
phenolphthalein in the presence of alkali. These pro-
cedures are low-selective, because their results can be
affected by oxidizing and reducing agents.
The drugs under consideration and the possible
impurities contain different functional groups and
therefore show different physicochemical properties.
In this connection, it seems appropriate to detect them
by such a quick, selective, and sensitive method as
thin-layer chromatography (TLC) .
The goal of this study was development of a pro-
cedure for detecting and separating impurities in Met-
azid and Ftivazide by TLC.
The test solutions of Metazid and Ftivazide were
prepared by dissolving 5 g of the preparation in 10 ml
of 95% ethanol (hereinafter, ethanol). The solutions
were subsequently filtered. Standard solutions of
INAH and vanillin were prepared by dissolving 0.01 g
of the substances in 100 ml of ethanol.
Structural features of Metazid, Ftivazide, and the
possible impurities suggest that the best sorbent for
their separation is silica gel. It is an acidic sorbent
allowing separation of substances that differ in acid3
base properties. In our studies we tested several
brands of silica gel.
The chromatograms were developed by UV irradia-
tion (l 254 nm). The detection sensitivity was 0.5 mg.
To choose the best mobile phase (MP), we studied
the chromatographic behavior of Metazid, Ftivazide,
INAH, and vanillin in a series of solvents. The results
are listed in the table. It is seen that the mobility of
the compounds increases with increasing solvent
polarity. Therefore, we chose as the major compo-
nents of the mobile phase chloroform and ethanol,
which significantly differ in the polarity. The compo-
sitions of the solvent systems and the results of chro-
matographic analysis of Ftivazide and Metazid are
given in Figs. 1 and 2.
Our results show that, in chloroform, vanillin is the
most mobile, and Ftivazide, Metazid, and INAH
show low mobility because of their poor solubility
(Figs. 1, 2, MP no. 1). Isonicotiic acid hydrazide in
chloroform shows the same chromatographic mobility
as Ftivazide and Metazid. In ethanol, all the com-
pounds are more mobile (Figs. 1, 2, MP no. 2). The
difference between the retention factors of Ftivazide
and INAH increases considerably, but the bands of
Ftivazide and vanillin become closer. The bands of
INAH and Metazid are separated, but DR
is as small
The subsequent experiments were performed with