Determination of Organic Volatile Impurities in Twenty-Three DifferentCoated Tablet Formulations Using Headspace Gas Chromatography withFlame Ionization Detection Technique

Abstract

Organic solvents are extensively used in manufacturing processes of pharmaceutical formulations that cannot be completely eliminated from the product due to physical and chemical barriers. These solvents have no therapeutic value and may be toxic to human body if intake exceeds the permitted daily exposure. Therefore, a simple and sensitive method for simultaneous determination of methanol, acetonitrile, methylene chloride, n-hexane, cyclohexane, xylene, chloroform, nitromethane, toluene and pyridine was developed and validated. Separation was achieved on HP-Innowax polyethylene glycol gas chromatographic column (30 m × 250 μm × 0.25 μm) using Agilent 7890B gas chromatograph equipped with Agilent 7697A headspace auto-sampler and flame ionization detector. Twenty-three marketed coated tablet formulations (containing diclofenac sodium, Loratadine or montelukast sodium as active ingredient) were tested for the presence of volatile organic impurities using this method. Excellent results were obtained, within the globally accepted validation reference values, particularly taking into account the low concentration levels were investigated in twenty-three coated tablet formulations.