Chemical stability of heparin, isopropanol, and ethanol line lock solutions

Background: Ethanol line locks are used in the US to prevent catheter associated bloodstream infections. Heparin precipitates in solution with ethanol. However, isopropanol may reduce precipitate formation. We aimed to determine the chemical stability of heparin, isopropanol, and ethanol line lock for a 10 day period at 2-8°C and 25°C.

Methods: Forty samples were prepared for analysis. Each sample was prepared identically using a 5 ml syringe capped with a Combi-stopper: 1 ml 70% isopropanol, 1 ml 70% ethanol, and 1 ml heparin sodium 10 IU/ml. Twenty syringes were stored at 2-8°C and 20 at 25°C. Analysis was carried out on days 1, 3, 6, 8, and 10 with a single syringe from each condition being tested in duplicate. Samples were assessed visually. Sub-visible particle count analysis was carried out using a CLIMET particle counting system. Heparin concentration was analysed using an anti-Xa assay. Ethanol and isopropanol concentrations were analysed by gas chromatography.

Results: Samples remained clear and colourless throughout the study. Sub-visible particle counts remained within limits specified in British Pharmacopoeia 2013 when stored at 2-8°C and 25°C, 60% humidity for up to 10 days. There was no significant change in ethanol or isopropanol concentration during the study. However, heparin activity fell by >10% after 1 day storage and to 65% of original activity after 10 days.

Conclusions: This study shows that addition of isopropanol to heparin and ethanol prevents precipitation. However, this solution shows a progressive decline in heparin activity over time making it unsuitable for extended shelf life.