Abstract
The narrow therapeutic index and significant toxicity of colchicine (COL) underscore the importance of content uniformity of dosage units to ensure drug safety and efficacy. In this study, transmission Raman spectroscopy (TRS) technology combined with partial least squares (PLS) regression was used for the non-destructive determination of low concentration levels of COL in commercial tablets (0.83 % w/w). Based on a multifactor orthogonal design of experiment, one hundred calibration tablets ranging in drug content from 70 % to 130 % of the label claim were manufactured to develop an initial model which was further calibrated using the HPLC results. The quantitative model displayed good repeatability and high accuracy with a root-mean-standard error for calibration of 0.038 % and root-mean-standard error for cross-validation of 0.039 %. The limits of detection and quantification were 0.13 % and 0.40 % w/w, respectively. The absolute value of relative error of the TRS and HPLC content results for commercial tablets varied between 0 and 3.8 %. Notably, the relative standard deviation (RSD) of the TRS method was 1.2 %, lower than the RSD of 2.9 % observed with HPLC. The results demonstrated a fast and non-destructive method for the quality control of highly toxic and low content active pharmaceutical ingredients in commercial products, without human or environmental exposure to toxic substances during sample preparation.