Detection of gabapentin-lactose maillard reaction product (Schiff's base): Application to solid dosage form preformulation / Part 1

Abstract

In the following study several techniques are utilized such as Differential Scanning Calorimetery (DSC), Infra-Red (IR) spectroscopy, High Performance Liquid Chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to characterize gabapentin (GBP) and lactose incompatibility in solid state binary mixtures and also in different capsule brands. Solid and aqueous mixtures of the drug and excipient were heated in order to prepare the adduct mixture. Based on the DSC results incompatibility was demonstrated and the imine formation was subsequently evaluated using FTIR spectra. HPLC analysis revealed two extra peaks (compound 1G and 2G) that were fractionated and then injected into LC-MS/MS system. Mass spectra of compound 2G was successfully correlated to GBP-lactose Maillard reaction product. The MRM (Multiple Reaction Monitoring) achieved using a new internal standard and was capable of detecting 4 separate peaks. The LC-MS/MS method was validated and then used for quantifying the amount of remaining drug in the test samples. The presence of lactose in commercial capsules was checked using a TLC method. Overall, the incompatibility of GBP with lactose was successfully evaluated using a combination of thermal methods, FTIR, HPLC and LC-MS/MS. آ© ECV آ· Editio Cantor Verlag.