Validated Stability Indicating LC Method for Carprofen: Characterization of Degradation Products by MS

Abstract

A simple, sensitive, and selective stability indicating high performance liquid chromatographic method has been developed and validated for quantitative analysis of carprofen (CPF) in presence of its degradation products. All degradation products in acid hydrolysis and photolysis were separated, identified by mass spectroscopic method and probable structures were elucidated. The forced degradation studies were performed on a bulk sample of CPF by using various methods like 0.1 M hydrochloric acid, 0.1 M sodium hydroxide, 0.33% hydrogen peroxide (H(2)O), heating at 60°C and exposure to UV light at 254 nm. A 5 μm particle octa desyl silane (ODS) column (150 mm × 4.6 mm) was used with acetonitrile-ammonium acetate (100 mM, pH-6.7) 40:60 (v/v) as a mobile phase at flow rate of 1.2 mL/min. Column oven temperature was maintained at 30°C and quantitation was achieved at 239 nm on the basis of peak area. The linear range and correlation coefficient (r(2)) was found 0.5-60 μg/mL and 0.9999 respectively. The limit of detection (LOD) and limit of quantitation (LOQ) were obtained 0.066 μg/mL and 0.20 μg/mL respectively . The proposed method was found to be suitable and accurate for quantitative analysis, stability study and characterisation of degradation product of CPF.

Photodegradation kinetics, transformation, and toxicity prediction of ketoprofen, carprofen, and diclofenac acid in aqueous solutions

“…For carprofen, the generation of transformation products mainly went through 3 transformation pathways (Figure B). A radical was formed by dechlorination, then CH 3 O• was reacted with the radical to form CAR‐2 , and H• was reacted with the radical to form CAR‐1. The carboxyl group of carprofen was esterified with methanol to generate the ester transformation product, which existed as a hydrochloric salt, namely CAR‐3.…”

“…Then the radicals may react with H•, HO•, and CH 3 O• and some other radicals to form transformation products [33,34]. For the chemicals containing a Cl atom on the benzene ring (carprofen and diclofenac acid), dechlorination is another important reaction type [35][36][37]. Oxidation of the benzene ring to form a phenolic hydroxyl group is also a universal reaction type in UV photolysis [38].…”