Abstract
A sensitive, accurate, precise and stability indicating HPTLC method has been developed and validated for the simultaneous determination of Paracetamol (PCT), Aceclofenac (ACF) and their impurities namely, 4-amino phenol (AP) and Diclofenac acid (DA), respectively, which are the hydrolytic degradation products and related substances of the drugs. The chromatographic separation was achieved using optimized mobile phase, ethyl acetate: methanol: glacial acetic acid (8.5:1.5:0.25 V/V) on pre-activated silica gel 60 F254 TLC plates with ultraviolet detection at 231 nm. Statistical analysis revealed linear relationships in the concentration ranges of 3900–9100, 1200–2800 for PCT, ACF respectively and 100-600 ng/band for AP and DA with correlation coefficient more than 0.99. The chromatographic conditions gave compact spots at Rf value (± SD) 0.60 (± 0.011), 0.21 (± 0.01), 0.83 (± 0.01) and 0.08 (± 0.015) for PCT, ACF, AP and DA respectively. The method was validated as per ICH guidelines, demonstrating to be accurate and precise within the corresponding linearity range of analytes. Inherent stability of these drugs was studied by exposing drug substances to stress conditions as per ICH guidelines namely oxidative, thermal, photolysis and hydrolytic conditions under different pH. Relevant degradation was found to take place under these conditions. PCT and ACF were found to undergo extensive acidic and basic hydrolysis while ACF was also susceptible to neutral hydrolysis; producing stated impurities as their major degradation products. The developed method resolved the drugs from degradation products generated under stress conditions; with the peak purity values greater than 0.999. Thus, a new simple, accurate, precise, sensitive and economic stability-indicating High Performance Thin Layer Chromatography (HPTLC)/densitometry method has been developed and validated for the simultaneous estimation of the titled analytes and their stated impurities in pharmaceutical dosage form. The high sensitivity and specificity make it valuable quantitative method suitable to be employed in the routine estimation of impurities and in stability studies.
Highlights
Paracetamol (PCT) is chemically N-(4-hydroxyphenyl) acetamide (Figure 1A). It is widely used as a minor analgesic, which is an alternative to aspirin without the side effects of salicylate on gastric mucosa [1]. 4-amino phenol (AP) (Figure 1C) has been found to be the primary hydrolytic degradation product of PCT
For the selection of optimized mobile phase to achieve sufficient resolution of PCT, ACF, their impurities and degradation products several runs were made by using mobile phases containing solvents of varying polarity in different proportion like toluene, chloroform, n-butanol, methanol, glacial acetic acid, formic acid, ethyl acetate, ammonia, acetone
The mobile phase consisting of ethyl acetate: methanol: glacial acetic acid (8.5:1.5:0.25 V/V) was found to give the optimum resolution with sharp well defined peaks at Rf value 0.60, 0.21, 0.83 and 0.08 for PCT, ACF, AP and diclofenac acid (DA) respectively
Summary
Paracetamol (PCT) is chemically N-(4-hydroxyphenyl) acetamide (Figure 1A). It is widely used as a minor analgesic, which is an alternative to aspirin without the side effects of salicylate on gastric mucosa [1]. 4-amino phenol (AP) (Figure 1C) has been found to be the primary hydrolytic degradation product of PCT. Paracetamol (PCT) is chemically N-(4-hydroxyphenyl) acetamide (Figure 1A) It is widely used as a minor analgesic, which is an alternative to aspirin without the side effects of salicylate on gastric mucosa [1]. Aceclofenac (ACF) is chemically 2-[2-[2-[(2,6- dichlorophenyl) amino]phenyl]oxyacetic acid (Figure 1B) It is used as an effective non-steroidal anti-inflammatory drug (NSAID) derived from the phenyl acetic acid in the relief of pain and inflammation in rheumatoid arthritis, ankylosing spondylitis and osteoarthritis [5]. It has pronounced anti-inflammatory, analgesic and antipyretic properties. The combination of PCT and ACF is available in the market for its synergetic effect in pain management
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