Open Access Research Article
Analytical & Bioanalytical
Techniques
Ali et al., J Anal Bioanal Tech 2014, 5:5
http://dx.doi.org/10.4172/2155-9872.1000211
Volume 5 • Issue 5 • 1000211
J Anal Bioanal Tech
ISSN: 2155-9872 JABT, an open access journal
Keywords: Allopurinol; Benzbromarone; TLC-Densitometric; RP-
HPLC
Introduction
1,5-Dihydro-4H-Pyrazolo[3,4-d]pyrimidin-4-one (Figure 1) [1],
known as Allopurinol (ALP), is an ofcial drug in British (BP) and
United States (USP) Pharmacopoeias [1,2] which is used for treatment
of gout and hyperuricaemia [3]. It is a xanthine oxidase inhibitor [4-
7], which prevents the oxidation of hypoxanthine to xanthine and
xanthine to uric acid [8]. Tus results in the reduction of urate and uric
acid concentrations in plasma and urine.
3,5-dibromo-4-hydroxyphenyl-2-ethyl-3- benzofuranyl methanone
(Figure 2) [1], known as Benzbromarone (BENZ), is an ofcial drug in
British (BP) Pharmacopoeia [1] which is used as a hypouricaemic drug. It
increases the excretion of uric acid by blocking renal tubular reabsorption
and thus reduces plasma concentrations and increases the excretion of uric
acid [9,10].
Combination of ALP and BENZ has the advantages of greater
therapeutic efect than with either drug alone [11]. Tis combination
causes manifold reduction in uric acid concentrations in plasma
and urine as compared to double dose of the individual drug when
used alone [12]. Also, this combination helps to decrease the dose of
each active ingredient, and as a result, decreases side efects of each
component if given separately in high doses [13].
Reviewing the literature in hand, only one report has been
published for determination of the studied mixture which depended
on measuring BENZ using zero order spectra at its λ
max
=356 while
ALP was determined by using (
2
D) amplitudes at 281.4 nm or by
measuring the amplitudes of the second derivative of the ratio spectra
curves (2DD) at 282.4 nm afer using a standard spectrum of 8 μgmL
-1
*Corresponding author: Weam Mahmoud Osman, Analytical Chemistry
Department, Faculty of pharmacy, Misr University for Science and Technology
(MUST), Egypt, Tel: 01004630203- 01117236884; E-mail: assem.wm@gmail.com
Received September 15, 2014; Accepted October 16 2014; Published October
20, 2014
Citation: Ali NW, Abdelwahab NS, Fatatry HMEL, Osman WM (2014) Development
and Validation of Different Chromatographic Methods for Determination of Two
Hypouricemic Drugs in Their Combined Dosage Form. J Anal Bioanal Tech 5: 211
doi:10.4172/2155-9872.1000211
Copyright: © 2014 Ali NW, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Abstract
Two sensitive, selective and precise chromatographic methods have been developed, optimized and validated for
Allopurinol (ALP) and Benzbromarone (BENZ) determination in their pure form, laboratory prepared mixtures and
pharmaceutical dosage form. The frst developed method was based on thin layer chromatographic (TLC) combined
with densitometric determination of the separated spots. The separation was achieved using silica gel 60F
254
TLC
plates. The mobile phase used was chloroform: methanol (9.2:0.8, v/v) and UV detection at 240 nm. Good correlations
were obtained between the integrated peak area of the studied analytes and their corresponding concentrations
in different ranges. The second developed method was based on the high-performance liquid chromatography
with ultraviolet detection, by which the proposed components were separated using Zorbax C
18
column using a
mobile phase consisting of sodium acetate buffer (pH=4.5, adjusted with acetic acid): acetonitrile : triethylamine
(50:50:0.5, by volume) maintaining the mobile phase fow rate at 1 mLmin
-1
with UV detection at 260 nm. Different
parameters affecting the suggested methods were optimized for maximum separation of the cited components.
System suitability parameters of the two developed methods were also tested. Validation of the methods has been
carried out according to USP requirements and ICH guidelines, accuracy, precision and repeatability were found to
be within the acceptable limits. The results obtained by TLC-Densitometric and RP-HPLC methods were statistically
compared with those obtained by the reported RP-HPLC method and no signifcant difference was found regarding
both accuracy and precision.
Development and Validation of Different Chromatographic Methods for
Determination of Two Hypouricemic Drugs in Their Combined Dosage Form
Nouruddin W Ali
1
, Nada S Abdelwahab
1
, Hamed M EL Fatatry
2
and Weam M Osman
2
*
1
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Bani-sueif University, Egypt
2
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Misr University for Science and Technology (MUST) 6th October, Egypt
(1H-pyrazolo [3,4-d]pyrimidin-4-ol)[1]
Figure 1: Allopurinol (ALP) structure.
(3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-3- benzofuranyl) methanone
Figure 2: Benzbromarone (BENZ) structure.