Development, Validation and Results of Quantitative Stability Testing for Gastrografin^®

Abstract

Introduction: Gastrografin® is a commercially available contrast agent, primarily utilised in abdominal computed tomography. In order to conduct a randomised controlled clinical trial to determine whether gastrografin® may confer a therapeutic benefit in a postoperative ileus it was necessary to ensure that re-packaging of gastrografin® during blinding had no effect on the stability of its active diatrizoate salts (DTZ). Aim: To develop a validated and rapid reverse phase High Performance Liquid Chromatography (HPLC) analytical method for the assay of DTZ that could then be utilised to determine the stability of gastrografin®. Methods: A published HPLC method for meglumine amidotrizoate injection was adapted and validated for the stability studies. These were carried out in accordance with ICH guidelines. Results: The HPLC method was validated for specificity (no elution peak with placebo), linearity (r2=0.999), accuracy (≤5%) and precision (≤3%). Gastrografin® exposed to 25ºC and 60% relative humidity remained stable for 30 days with no physical change to the solution. Gastrografin® stored under identical conditions and exposed to 1.2 million lux hours of light remained stable for 7 days. Gastrografin® stored at 4ºC underwent crystallisation; this was readily reversed by agitation and had no discernible effect on 30-day drug stability. Conclusion: Gastrografin® remains stable and active for a minimum of 30 days under standard storage conditions (25ºC, 60% humidity, no light) after re-packaging.