African Journal of Pharmacy and Pharmacology Vol. 5(3), pp. 298-305, March 2011
Available online http://www.academicjournals.org/ajpp
DOI: 10.5897/AJPP10.083
ISSN 1996-0816 ©2011 Academic Journals
Full Length Research Paper
Stability-indicating (liquid chromatographic) LC method
for the determination of rifabutin in bulk drug and in
pharmaceutical dosage form
Jaiprakash N. Sangshetti, Sachin Hingankar, Amol Waghule and Devanand B. Shinde*
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, India.
Accepted 15 March, 2011
A novel stability-indicating LC assay method was developed and validated for quantitative
determination of Rifabutin in bulk drugs and in pharmaceutical dosage form in the presence of
degradation products generated from forced degradation studies. An isocratic, reversed phase LC
method was developed to separate the drug from the degradation products, using an Ace5-C18 (250 x
4.6 mm, 5 μm) column, and 50 mM ammonium acetate (pH-4 by acetic acid) and acetonitrile (50:50v/v) as
a mobile phase. The detection was carried out at the wavelength of 275 nm. The Rifabutin was
subjected to stress conditions of hydrolysis (acid, base), oxidation, photolysis and thermal
degradation. Degradation was observed for Rifabutin hydrolysis (acid, base), oxidation and photolysis
conditions attempted. There is no degradation in thermal condition. The degradation products were well
resolved from the main peak. The percentage recovery of Rifabutin ranged from (99.42 to 100.27%) in
pharmaceutical dosage form. The developed method was validated with respect to linearity, accuracy
(recovery), precision, specificity and robustness. The forced degradation studies prove the stability-
indicating power of the method.
Key words: Rifabutin, column liquid chromatography, stability indicating method, validation.
INTRODUCTION
Rifabutin is chemically known as (Figure 1; 4-deoxo-3, 4-
[2-spiro-(N-iso- butyl - 4 - piperidyl) - 2, 5 - dihydro - 1H -
imidazo] - rifamycin-S), a semisynthetic derivative of
rifampicin S, that has shown broad-spectrum antibacterial
activity against Gram-positive and Gram-negative
organisms, including mycobacteria. Rifabutin was found
to have activity against Mycobacterium avium-
intracellular isolated from patients with AIDS (Heifets,
1987) has been approved for prophylaxis of combination
therapy containing rifampin.Disseminated Mycobacterium
avium complex (MAC) in patients infected with human
immunodeficiency virus (HIV). Prophylactic treatment
with rifabutin was shown to decrease the incidence of
MAC by approximately 50% in AIDS patients enrolled in
two randomized, placebo - controlled clinical trials
*Corresponding author. E-mail: dbsjaiprakash05@rediffmail.
com.
(Nightingal, 1993). Rifabutin (Rfb) is a bactericidal
antibiotic drug primarily used in the treatment of
tuberculosis. Its effect is based on blocking the DNA-
dependent RNA-polymerase of the bacteria. It is effective
against Gram-positive and some Gram-negative bacteria,
but also against the highly resistant Mycobacteria, e.g.
Mycobacterium tuberculosis, Mycobacterium leprae and
Mycobacterium avium intracellulare.
A recent literature survey revealed that few methods
were available for the determination of rifabutin in bio-
logical samples, which involved high performance liquid
chromatography (HPLC) with UV detection (Lau, 1996;
Gatti, 1999). According to current good manufacturing
practices, all drugs must be tested with a stability-
indicating assay method before release. Literature survey
reveals that there is no stability-indicating LC assay
method for determination of Rifabutin in bulk drug and
pharmaceutical dosage form. In the present research
article, we report the development and validation of a
stability-indicating LC method for the determination of