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Ph.D.
(Pharmacy)
DEVELOPMENT AND VALIDATION OF ANALYTICAL METHODS AND
IMPURITY PROFILING FOR SOME ANTIHYPERTENSIVE DRUGS IN
DOSAGE FORMS
Ph.D. Scholar : Alpa Chiragkumar Sheth
Research Supervisor : Dr. Paresh U. Patel

Regi. No.: 17276011003
Abstract :
The present work represents a specific, stability-indicating, accurate and precise method
for impurity profiling by RP-HPLC method and Elemental Impurities in anti-hypertensive
drugs dosage forms. Identify and characterized the degradation impurities with different
techniques like IR, Mass spectroscopy, and 1H NMR Spectroscopy obtained by the RP-
HPLC method. The determination of Organic impurities stability indicates the method is
developed by RP-HPLC for Phenoxybenzamine Hydrochloride dosage form. Identify and
characterized the degradation impurities i.e. 2-[benzyl(1-phenoxypropan-2-
yl)amino]ethan-1-ol-Hydrochloride and 1-benzyl-1-(1-methyl-2-phenoxy-2-ethyl)-
aziridiniumperchlorate which is present in Phenoxybenzamine Hydrochloride dosage
form. Class I and II A Elemental impurities are determined and quantified by the ICP-MS
method as per ICH Q3 (D) guideline and USP chapter <233>for Phenoxybenzamine
Hydrochloride dosage form. The specification limit of each elemental impurity (Vanadium,
Cobalt, Nickel, Arsenic, Cadmium, Mercury, and Lead) is selected based on the Permitted
daily exposure of finished product dosage form label claim i.e. 10 mg.The degradation
study was carried out under different environments like acidic, alkaline, neutral, oxidative,
photolytic, humidity, and thermal conditions. The developed organic impurities method
was validated in terms of specificity, linearity, range, accuracy, precision, robustness, the
limit of detection, the limit of quantitation, repeatability, and system suitability as per ICH
Q2 (R1) guidelines. The developed elemental impurities method was validated in terms of
specificity, linearity, range, accuracy, precision,limit of detection, the limit of quantitation,
repeatability, and system suitability as per ICH Q2 (R1) guideline and USP chapter <233>.

The calibration curve of all the developed methods was found linear over the proposed
concentration range. Percentage impurity profiling and Percent recoveries of the same
were obtained within the limit specified as per ICH guidelines. The stability indicating RP-
HPLC method was able to detect and/or separate the drugs from their degradants. All the
developed methods were found simple, sensitive, accurate, precise, and robust and can
be utilized for the routine quantitative analysis of selected drug formulation.

Key words: Impurity profiling, Elemental Impurities, ICP-MS, Permitted daily exposure.

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