Abstract
A simple, rapid, and sensitive RP-HPLC method was developed and validated for the simultaneous determination of chlordiazepoxide (CDO) and mebeverine HCl (MBV) in the presence of CDO impurity (2-amino-5-chlorobenzophenone, ACB) and MBV degradation product (veratric acid, VER). Separation was achieved within 9 min on a BDS Hypersil phenyl column (4.5 mm × 250 mm, 5 µm particle size) using a mobile phase consisting of acetonitrile: 0.1 M potassium dihydrogen phosphate: triethylamine (35 : 65 : 0.2, v/v/v) in an isocratic mode at a flow rate of 1 mL/min. The pH of the mobile phase was adjusted to 4.5 with orthophosphoric acid and UV detection was set at 260 nm. A complete validation procedure was conducted. The proposed method exhibited excellent linearity over the concentration ranges of 1.0–100.0, 10.0–200.0, 2.0–40.0, and 2.0–40.0 µg/mL for CDO, MBV, VER, and ACB, respectively. The proposed method was applied for the simultaneous determination of CDO and MBV in their coformulated tablets with mean percentage recoveries of 99.75 ± 0.62 and 98.61 ± 0.38, respectively. The results of the proposed method were favorably compared with those of a comparison HPLC method using Studentt-test and the variance ratioF-test. The chemical structure of MBV degradation product was ascertained by mass spectrometry and IR studies.
Highlights
Chlordiazepoxide (CDO, Figure 1(a)), 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide, is a benzodiazepine with general properties similar to those of diazepam
We developed a stability-indicating HPLC method for the analysis of CDO and mebeverine HCl (MBV) in combination and in the presence of MBV degradation product (VER) and CDO synthetic precursor and main impurity (ACB)
Separation was performed on a BDS Hypersil phenyl column (4.5 mm × 250 mm, 5 μm particle size) from Thermo Electron Corporation (Runcorn, UK), using a mobile phase consisted of a ternary mixture of acetonitrile: 0.1 M potassium dihydrogen phosphate: TEA (35 : 65 : 0.2, v/v/v)
Summary
Chlordiazepoxide (CDO, Figure 1(a)), 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide, is a benzodiazepine with general properties similar to those of diazepam. The USP [3] describes HPLC methods for its determination in pure form and single or coformulated tablets with either clidinium bromide or amitriptyline HCl. Literature survey revealed many analytical methods for the determination of CDO either alone or in combination with other drugs. Our main target was to develop a simple, sensitive, and rapid isocratic stabilityindicating HPLC method for the simultaneous determination of the two drugs in their combined tablets in the presence of their degradation products or synthesis impurities. We developed a stability-indicating HPLC method for the analysis of CDO and MBV in combination and in the presence of MBV degradation product (VER) and CDO synthetic precursor and main impurity (ACB). The proposed procedure is suitable for the quality control analysis and purity assessment of dosage forms containing the two studied compounds
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
