Original Article
A NOVEL VALIDATED UHPLC METHOD FOR ESTIMATION OF ASSAY AND ITS RELATED
SUBSTANCES OF TRICHOSTATIN-A
L. VAIKUNTA RAO
1*
, K. TIRUMALA RAO
1,2
, V. V. KRISHNA MOHAN KANDEPI
2
1
Department of Chemistry, Gitam Institute of Science, GITAM University (Deemed to be), Visakhapatnam 530045, India,
2
Product and
Technology Development, Eco Logic Technologies Ltd, Hyderabad 500072, India
Email: tirumalwithu@gmail.com
Received: 19 Feb 2020, Revised and Accepted: 21 May 2020
ABSTRACT
Objective: The main objective of the research work is to develop and validate a rapid UHPLC method for the estimation of assay and its related
substances of Trichostatin A (TSA) in pharmaceutical samples.
Methods: The UHPLC method developed for chromatographic separation between TSA and its related compounds on Poroshell 120 SB C18(50×4.6)
mm; 2.7 µm RRLC column using Agilent RRLC (UHPLC) system with linear gradient elution.
Results: The developed UHPLC method has shown excellent chromatographic separation between TSA and its related compounds within 12 min
run time, during validation experiments, specificity study revealed that the peak threshold was more than the peak purity and no purity flag was
observed. Repeatability, intra, and inter-day precision results were well within the tolerable limits. Limits of detection concentrations were found
between 0.075 to 0.077 ppm and the limit of quantitation is between 0.252 to 0.258 ppm for related compounds and TSA. The related substances
method recoveries were found between 80 and 120 % and assay method recovery was found between 98.0 to 102.0%.
Conclusion: The developed method capability was proven for the assay of TSA and its related compounds in pharmaceutical samples and the
method shows eco-friendlier than routine, conventional HPLC methods in terms of analysis time, cost and HPLC effluent waste.
Keywords: Trichostatin A, Assay, Related substances, Method Validation, RRLC, UHPLC
© 2020 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijpps.2020v12i7.37198. Journal homepage: https://innovareacademics.in/journals/index.php/ijpps
INTRODUCTION
The HPLC method is an analytical method in which proving the
separation-related impurities and its drug compound, and it helps to
estimate the content of impurities and drugs to prove the quality of
the drug substances [1-3]. In this study used UHPLC system and
short column during development and the application of the UHPLC
method is chromatographic method gained increasing importance
because of their high selectivity, sensitivity and quick
chromatographic separation method. In order to prove the quality of
the drug substance being analyzed in sample solutions, it is
necessary to measure the amount of impurities and drugs. By
applying UHPLC concepts, it can reduce the run times of
chromatographic methods and effluents and decrease the
turnaround times [4-6]. Various UHPLC methods have been
developed for the determination of related compounds and potency
of the drug in pharmaceutical drug substances and formulations and
many bioanalytical methods were developed to estimate the drug
content in the pharmacy kinetic study and dietary samples [7-10].
Trichostatin A (TSA) is chemically known as, [R-(E,E)]-7-[4-
(Dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-Oxo-2,4-hepta-
dienamide (fig. 1). Trichostatin A is a hydroxamic acid. It has a role
as a bacterial metabolite. It derives from a (R)-Trichostatic acid. TSA
serves as an antifungal antibiotic and selectively inhibits the class I
and II mammalian histone deacetylase (HDAC) families of enzymes,
but not class III HDACs (i.e., sirtuins) [11, 12]. It is a member of a
larger class of histone deacetylase inhibitors (HDIs or HDACIs) that
have a broad spectrum of epigenetic activities. Thus, TSA has some
potential as an anti-cancer drug [13, 14].
Fig. 1: Chemical structure of trichostatin A (TSA)
TSA concentration was determined by high-performance liquid
chromatography (HPLC)-UV assay (high dose) or by HPLC-multiple
reaction monitoring assay (low dose) in plasma sample [15] and
identification of the TSA by IEX-HPLC [16] and reported on stress
studies of HDAC family compound YK-1101by HPLC–UV and HPLC–
TOF/MS methods [17] and also the majority of the reports were
published on drug activity and metabolism [18-20].
Screening the literature, no related substances and assay method
has been reported for the determination of TSA in pharmaceutical
International Journal of Pharmacy and Pharmaceutical Sciences
Print ISSN: 2656-0097 | Online ISSN: 0975-1491 Vol 12, Issue 7, 2020