Different stability-indicating chromatographic methods for specific determination of paracetamol, dantrolene sodium, their toxic impurities and degradation products

A well-known analgesic (paracetamol, PAR) and skeletal muscle relaxant [dantrolene sodium (DNS)] have been analyzed without interference from their toxic impurities and degradation products. The studied PAR impurities are the genotoxic and nephrotoxic p-amino phenol (PAP) and the hepatotoxic and nephrotoxic chloroacetanilide, while 5-(4-nitrophenyl)-2-furaldehyde is reported to be a mutagenic and carcinogenic degradation product of DNS. The five studied components were determined and quantified by TLC-densitometric and RP-HPLC methods. TLC-densitometry (method 1) used TLC silica gel and chloroform-ethyl acetate-acetic acid-triethylamine (7:3:0.5:0.05, by volume) as the mobile phase with UV scanning at 230 nm, while RP-HPLC (method 2) was based on separation on a C-18 column using methanol-water (55:45, v/v pH 3 with aqueous formic acid) as mobile phase at 1 mL/min and detection at 230 nm. The developed methods were used for determination and quantification of the five studied components in different laboratory-prepared mixtures. The were also applied for analysis of Dantrelax (R) compound capsules where no interference among the studied components with each other or from excipients was observed. The methods were validated as per International Conference on Harmonization guidelines, and they compared favorably with the reported ones.