Stability studies of etoposide as syringes for intrathecal administration and syringes for pediatric oral administration

Abstract

Introduction

In pediatric practice, etoposide is a cytotoxic drug that can be prescribed under various routes of administration according to the indication. These prescriptions can imply frequent preparations, which can be secured through batch production and storage. However, this practice requires stability data.

Methods

The HPLC-UV dosing method of etoposide and its degradation products was validated. Validation of microbiological analyses was also performed. All relevant parameters were also studied (particle contamination, pH, leachables, but also preservative efficacy and benzaldehyde content for oral etoposide and endotoxin for intrathecal etoposide.

Results

10 mg.mL⁻¹ etoposide for oral administration, both in normal saline or in dextrose 5% was proven to be stable for 15 days when stored at 25°C/60% RH and 90 days at 2–8°C. 0.1 mg.mL⁻¹ etoposide for intrathecal administration was stable in Luer-Lock syringes for 2 days when stored at 25°C/60% RH and 14 days at 2–8°C, and in NRFit^® syringes for 14 days both when stored at 25°C/60% RH and at 2–8°C.

Conclusions

Etoposide 10 mg·mL^–1 for oral administration must be prepared under strict aseptic conditions and can be stored for 15 days at ambient temperature and 90 days under refrigerated conditions. Etoposide 0.1 mg·mL^–1 for intrathecal administration in normal saline should be compounded in NRFit^® syringes and can be stored for 14 days under refrigerated conditions. This study demonstrates that the container–closure system is an integral component of the drug product, as syringe type significantly influences impurity formation and leachable release, with direct implications for pharmaceutical quality and safety.