Development and Validation of RP-

HPLC Method for the Estimation of

Trimetazidine in Bulk and
Pharmaceutical Dosage Form.

By: [Student Name]

Guide: (Name of Guide)
Department:
Year:
 Content
• Introduction
• Objective
• Plan of Work
• References
 Introduction
• Analytical method plays an important role in the discovery, development and manufacturing of
pharmaceuticals. The aim of method development is to develop analytical method for drug product
containing active ingredient to allow accurate and precise quantitation of drug 1, 2.
• The objective of the analytical procedure should be clearly understood since this will govern the
validation characteristics which need to be evaluated. Typical validation characteristics which
should be considered are listed below[3]:
Accuracy
Precision
• Repeatability
• Intermediate Precision
Specificity
Detection Limit
Quantitation Limit
Linearity
Range
 Trimetazidine
• Trimetazidine is an orally available small molecule compound with anti-ischemic,
and potential immunomodulating and antineoplastic properties.
• Although its exact mechanism is not yet fully elucidated, it is postulated that upon
administration, trimetazidine selectively inhibits long-chain 3-ketoacyl coenzyme A
thiolase (LC 3-KAT), the final enzyme in the free fatty acid (FFA) beta-oxidation
pathway.
• This stimulates glucose oxidation, which requires less oxygen usage and cellular
energy than in the beta-oxidation process. This optimizes myocardial energy
metabolism and cardiac functioning in an ischemic condition.
• In cancer cells, the inhibition of fatty acid oxidation (FAO) alters the metabolic
processes needed for tumor cell function and proliferation, thereby inducing tumor
cell apoptosis.
• In addition, inhibition of FAO may potentially block the immunosuppressive
functions of myeloid-derived suppressor cells (MSDCs), which are thought to
promote malignant cell proliferation and migration by inhibiting T-cell function.
• Its molecular formula is C14H22N2O3, and its molecular weight is 266.34 g/mol. [4]
Structure of Trimetazidine
• 1-(2,3,4-Trimethoxybenzyl)piperazine is the chemical name for
Trimetazidine. It is white to off-white powder. It is soluble in acetonitrile,
di methyl formamide, di methyl sulphoxide. It is an anti-ischemic (anti-
anginal) metabolic agent.[5]
• In literature review, various methods are available for determination of
Trimetazidine by RP- HPLC. [6-8] The present work, is therefore focused on
to achieve the optimum chromatographic conditions for the determination
of Trimetazidine in a formulation by RP-HPLC method, And validate
according to ICH guidelines.
 Objective
• To develop and validate RP-HPLC method for
estimation of Trimetazidine in bulk & dosage form.
 Plan of Work
• Review of literatures.
• Procurement of active pharmaceutical ingredient,
dosage form, chemicals, and solvents, etc.
• Development of analytical method, for estimation of
Trimetazidine in bulk and dosage form.
• Validation of method as per ICH guidelines.
• Dissertation writing/publication.
 References
1. Analytical Method Development [Internet]. [cited 2020 Aug 8]. Available from:
http://shodhganga.inflibnet.ac.in/bitstream/10603/8513/9/09_chapter%202.pdf
2. Aim and objective [Internet]. [cited 2020 Aug 8]. Available from:
http://shodhganga.inflibnet.ac.in/bitstream/10603/54485/5/chapter%202.pdf
3. Validation of Analytical Procedures: Text and Methodology; Guidline Q2(R1); International Conference
on Harmonisation(ICH);November 2005; Page No. 1-13.
4. Trimetazidine [Internet]. Pubchem. [Last accessed on 11-06-2021]. Available From:
https://pubchem.ncbi.nlm.nih.gov/compound/Trimetazidine
5. Trimetazidine [Internet]. Wikipedia. [Last accessed on 11-06-2021]. Available From:
https://en.wikipedia.org/wiki/Trimetazidine#:~:text=Trimetazidine%20is%20an%20anti%2Dischemic,inhi
bition%20of%20fatty%20acid%20metabolism
.
6. Thoppil, S. O., & Amin, P. D. (2001). Trimetazidine: stability indicating RPLC assay method. Journal of
pharmaceutical and biomedical analysis, 25(2): 191–195.
7. Naushad, M.A., Aqil, M., Ahmad, F.J. et al. Development and validation of the HPLC method for the
analysis of trimetazidine hydrochloride in bulk drug and pharmaceutical dosage forms. J Anal Chem.
2008; 63: 965–970. 
8. Venisetty, Raj Kumar & Nagula, Sreelatha & Thota, Sridhar. Development and validation of a stability
indicating RP-HPLC method for the determination of trimetazidine dihydrochloride. Der Pharma
Chemica. 2014; 6: 149-154.