RP-LC gradient elution method for simultaneous determination of thiocolchicoside, aceclofenac and related impurities in tablet formulation

Abstract

Objective:The aim of the present study is to develop a simple and precise HPLC method for simultaneous determination of thiocolchicoside, aceclofenac and related impurities in a tablet formulation and validate as per ICH guidelines. The aim of study extends to perform forced degradation study to trace the degradation pathways of potential degradant impurities.Materials and Methods:The separation was achieved on a 4.6 mm × 100 mm, 3 μm C18 column at 40°C with the mobile phase containing 0.1 M ammonium acetate buffer and methanol in a gradient mode at a flow rate of 1.0 mL min−1. The UV detection was carried out at 257 nm.Results:Acelofenac, thiocolchicoside and their related compounds were well separated from each other with good resolution and symmetry factor without interference of excipients. The method for assay was linear in the range of 10-200 μg mL−1 for aceclofenac and 0.4 to 8 μg mL−1 for thiocolchicoside.Conclusion:The method was validated according to ICH guidelines and the acceptance criteria for accuracy, precision, linearity, specificity, robustness, ruggedness and system suitability were met in all cases. The method was highly specific, as two related compounds of thiocolchicoside and nine related compounds of aceclofenac were well separated from each other. Stress study ensured the specificity of the method as the unknown degradation products formed during stress studies did not interfere with the determination of thiocolchicoside and aceclofenac, thus proving the stability indicating capacity of the method.

Isolation and Structural Characterization of Degradation Products of Aceclofenac by HPLC, HRMS and 2D NMR

“…The compound was already reported earlier as a degradant. However, its spectra data is not published [14]. H NMR spectrum revealed that DP-3 had 7 aromatic protons, 1 aliphatic CH2 group, two exchangeable protons of one NH and one carboxylic acid.…”

“…All the products were selectively separated and fully characterized by various 2D NMR and mass spectroscopic methods experiments. The degradation products DP-2 and DP-3 were reported as the impurities of aceclofenac [9][10][11][12][13][14]. However, to the best of our knowledge, this is the first report on the structure characterization of degradation product (DP-2).…”

“…The study showed that the degradant formed is diclofenac by comparison of its standard chromatogram in both acidic and basic stress conditions [9]. Other reports [10][11][12][13][14][15] were found on simultaneous estimation of aceclofenac along with other NSAIDs by HPLC . All the above cited literature revealed that the drug is unstable under various stress conditions tested and few other degradants were formed.…”

Optimization of HPLC method using central composite design for estimation of Torsemide and Eplerenone in tablet dosage form

“…2017), Voltametric method (Fernández et al, 1994), Spectrophotometric methods (Bagade,Patil, 2010;Krishna, Sankar, 2008;Golher, Kapse, Singh, 2010), RP HPLC (Zaazaa et al,.2016;Jovic et al, 2012;Ghodke, Poul, Sorde, 2014;Khan, Loya, Saraf, 2008;Shukla et al, 2012), RP-LCMS (Zhang et al, 2016;Jovic et al, 2012), Thermal method (Rollinger et al, 2003) and HPTLC (Kakde et al, 2011) method for determination of TOR in pharmaceutical dosages were developed. TOR was estimated, with other antihypertensive drugs Spironolactone, Moxifloxacin, Levofloxacin, Gemifloxacin and Pseudoephidrine using spectrophotometric methods from bulk and pharmaceutical dosage forms (Reddy, Sayanna, Venkateshwarlu.,2014;Bhadja et al, 2014a;Golher,Kapse,Singh, 2010;Sharma et al, 2010b;Sasikala, Sayanna, Venkateshwarlu, 2015) and also with Spironolactone and Amiloride using the RP -HPLC method in binary mixtures (Deshpande et al, 2012;Bhalodiya, Modiya, Faldu, 2014;Bihola, Prajapati, Agrawal, 2018;Dubey et al, 2012;Laxman et al, 2010), The stability indicating RP HPLC method for the determination of TOR with Spironolactone in bulk and pharmaceutical product (Karbhari, Bhoir,Joshi, 2013). HPTLC method is used for simultaneous estimation of TOR with spironolactone and amiloride (Sharma et al, 2010b;Bhadja et al, 2014b;Gaikwad et al, 2010).…”

A green HPLC method for the determination of torasemide in pharmaceutical dosage forms: Development, validation, and greenness assessment

“…Analytical procedures previously published in the literature were scanned to determine the amount of TSD in bulk and pharmaceutical dosage forms and biological fluids. Spectrophotometric [19][20][21][22][23][24][25][26], voltammetric [27], capillary electrophoresis [28], high-performance liquid chromatographic [29][30][31][32][33][34][35][36][37][38][39][40], liquid chromatographic coupled with tandem mass spectrometry (LC-MS/MS) [40,41], thermal [42], and high-performance thin-layer chromatography [43][44][45][46] methods were reported for determination of TSD in bulk and pharmaceutical dosage forms and biological fluids were developed.…”