Development and validation of a stability-indicating RP-HPL C-CAD method for gabapentin and its related impurities in presence of degradation products

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 125; pp. 122 - 129
• Main Authors: Ragham, Pramod Kumar, Chandrasekhar, Kothapalli B.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.06.2016
• Subjects: Amines - analysis; Chromatography, High Pressure Liquid - methods; Chromatography, Reverse-Phase - methods; Corona charged aerosol detector (CAD); Cyclohexanecarboxylic Acids - analysis; Forced degradation; Gabapentin; gamma-Aminobutyric Acid - analysis; Related substances; Spectrometry, Mass, Electrospray Ionization; Stability-indicating assay; Corona charged aerosol detector (CAD); Related substances; Gabapentin; Forced degradation; Stability-indicating assay
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2016.03.035

Degradation pathway for Oxidative stress degradation impurities. [Display omitted] •As per the literature survey, we have found that there are lots of UV methods are published for non chromophoric Gabapentin. Where it lacks the sensitivity with respect to the quantification and identification of potential Impurities.•We have developed a method using Novel Universal Corona charged aerosol detection system which is sensitive and selective. It is a LC–MS compatible method which can be directly used for identification of degradation impurities.•The same method was completely validated with respect to all the parameters as per regulatory guideline requirements.•Even efforts are made to understand the stress degradation of Gabapentin drug substances and the degradation impurity was identified and reported by LC–MS/MS studies. The objective of the current study was to develop and validate a sensitive and specific LC–MS compatible stability indicating reversed phase liquid chromatographic method for the quantitative determination of Gabapentin and its related substances using Corona charged aerosol detection (CAD). The chromatographic conditions were optimized using a Kinetix Biphenyl column with gradient elution using a mobile phase composed of pH 4.2 ammonium acetate, acetonitrile, and methanol. Forced degradation was observed in basic and peroxide conditions and the major degradants were identified by LC–MS/MS analysis. The developed RP-HPLC CAD method was validated according to ICH guidelines. The LOD and LOQ values for Gabapentin and all its related impurities ranged from 0.075μg/mL to 0.18μg/mL and 0.25μg/mL to 0.60μg/mL, respectively. The recovery for all impurities ranged from 91.0 to 105.6%w/w. Solutions were stable for 7days at room temperature. The validated method produced acceptable precision, linearity, accuracy, robustness and ruggedness.