ISSN 1061-9348, Journal of Analytical Chemistry, 2009, Vol. 64, No. 7, pp. 714–720. © Pleiades Publishing, Ltd., 2009.
714
1
Sulfanamides are N1-substituated derivates of
p-aminobenzenesulfonamide (sulfanilamide) [1] and
commonly used to combat a variety of bacteria [2]. Sul-
famethoxazole, a derivate of sulfonamide, has been
also widely used to treat the Acquired Immunodefi-
ciency Syndrome (AIDS) but it can occasionally cause
adverse reactions such as delayed-type hypersensitivity
and hepatitis [3]. Metal complexes of aromatic/hetero-
cyclic sulfonamides act as stronger inhibitors of the
zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as
compared with the uncomplexed sulfonamides [4].
Several low nanomolar mitochondrial isozyme car-
bonic anhydrase (CA) V (murine origin) inhibitors
were detected such as acylated sulfanilamide, ureido-
benzenesulfonamide, 1,3,4-thiadiazole-2-sulfonamide
and aminobenzolamide type of compounds [5]. Sulfan-
amides are especially used for vaginal infection since
they are rapidly absorbed through the vaginal mucosa;
however, the mechanism of absorption is not known
yet. Bristol et al. reported that the use of sulfanilamide
as vaginal cream in the cervical cancer induced methe-
moglobinemia by an unknown mechanism [6].
Kauffman et al. determined herbicide asulam and its
antibacterial active metabolite sulfanilamide in honey
with liquid chromatography—tandem mass spectrome-
try (LC-MS/MS) [7]. The authors explained this situa-
tion by that bees occasionally collect nectar from mead-
ows treated with asulam. Such honeys were not only
contaminated with asulam but also by its degradation
1
The article is published in the original.
product sulfanilamide [7]. According to the results of
Reybroeck [8], sulfanilamide was detected among
48 imported honey samples available in Belgian mar-
kets. In this research, the limits of quantification for sul-
fonamides (sulfaguanidine, sulfanilamide, sulfaceta-
mide, sulfadiazine, sulfathiazole, sulfadimidine, sul-
famethoxazole) were found to be 20 μg/g.
It is also necessary to determine the sulfanilamide
content in human liquids like urine. The exposure to
sulfanilamide by consumption of contamined honey
may be a problem for health.
To determine the concentrations of sulfanamides
and its derivates, various analytical methods have been
developed. These include ultraviolet-spectrophotome-
try [9], capillary supercritical fluid chromatography—
Fourier transform infrared spectroscopy (cSFC-FT-IR)
[2], high performance liquid chromatography (HPLC)
[1, 10, 11], LC-MS/MS [7], liquid chromatography
[12], capillary electrophoresis (CE) [13] and flow
injection-spectrophotometric detection [14]. The major
disadvantage of HPLC for the determination of the res-
idues of sulfanilamides in complex matrices is that an
extensive clean-up step is needed prior to analysis. GC
methods have been shown to be sensitive and specific
but the nonvolatile nature of sulfanamides means that
conversion to the N
1
-methyl or N
1
-acyl derivatives is
required [2].
Moreover, none of above mentioned methods is a
stability-indicating method. The International Confer-
ence on Harmonization (ICH) guideline entitled ‘sta-
ARTICLES
Stability-Indicating High Performance Thin Layer
Chromatographic Determination of Sulfanilamide
in Human Urine
1
E. Kilinc, B. Gumgum, C. Hamamci, and F. Aydin
Department of Chemistry, Faculty of Art and Science, University of Dicle, Diyarbakir, TR-21280 Turkey
e-mail: ekilinc@dicle.edu.tr
Received December 20, 2007; in final form December 4, 2008
Abstract—A simple, sensitive, selective, precise and stability-indicating high-performance thin-layer chro-
matographic (HPTLC) method was developed and applied to human urine for the densitometric determination
of sulfanilamide. A mixture of chloroform-ethyl acetate-xylene (2.5 : 4.0 : 1.0, v/v/v) was used as a mobile
phase. The system was found to give compact spots for sulfanilamide (retardation factor, R
f
= 0.21 ± 0.02). The
linear regression analysis data for the calibration plots showed good linear relationship with r
2
= 0.9970 ±
0.0003 and r
2
= 0.9947 ± 0.020 within the concentration range of 50–250 ng per spot and 100–1000 ng per spot
with respect to peak area, respectively. The limit of detection (LOD) and quantification (LOQ) were 8 and
25 ng per spot, respectively. Sulfanilamide was subjected to acid and alkali hydrolysis, oxidation, dry heat and
wet heat treatment. According to the International Conference on Harmonization (ICH) guidelines the method
was validated for precision, recovery and robustness. The ultraviolet (UV) spectra of the degradation products
which had different spectra from sulfanilamide were also recorded.
DOI: 10.1134/S1061934809070090