Long term and simulated in-use stabilities of irinotecan chemotherapy polyolefin infusion bags in dose banding conditions

Abstract

Purpose

The dose-banding of irinotecan provides the opportunity to anticipate the preparation of this anticancer drug on condition of carrying out stability studies. The aim of this study was to develop and validate a HPLC method for measuring the concentration of irinotecan and to evaluate its long-term stability at standardized rounded doses in polyolefin (POF) infusion bags at 4°C and protected from daylight. Microbiological and Physical stability tests were periodically performed including visual inspection, turbidity, lightness and chromaticity measurements. In addition, in a simulated in-use study, irinotecan quantification was also performed on the solution emitted from the POF infusion bags on a short period (24 h), at room temperature (25°C) and in daylight.

Methods

The HPLC with photodiode array (PDA) detector method was developed and validated (linearity, precision, accuracy, limits of detection and quantification, robustness and degradation test). Diluted irinotecan infusion solutions were aseptically prepared by further dilution of irinotecan stock solution with 0.9% sodium chloride in POF bags at banded doses 200 mg, 300 mg and 370 mg, the three most frequently produced doses in the pharmacy department. The POF bags were stored under refrigeration (4°C) in the dark (long term stability conditions) or at room temperature (25°C) in daylight for a short period 24 h (simulated in-use conditions). Microbiological tests were carried out and the physical and chemical stabilities were evaluated respectively through visual inspection, turbidity, lightness, chromaticity measurements and through chromatographic assays, pH and osmolality monitoring.

Results

The long - term stability of irinotecan at selected standardized rounded doses (200 mg–300 mg–370 mg) in NaCl 0.9% polyolefin bags was confirmed for at least 84 days at 4 °C and in the dark. Microbiological tests performed on the samples were negative. As well, during the simulated in-use study, no signs of chemical instability were observed.

Conclusions

A simple, accurate and stability-indicating HPLC method was developed to determine irinotecan concentrations in dose-banding conditions. As well, this present work including HPLC peak width, lightness and chromaticity measurements of a cytotoxic drug during the time of storage may be a guidance in stability studies. This study supports a centralized production of irinotecan in accordance with the studied conditions.