Researchers in Germany have developed a new assay for heparin which can detect not only oversulphated chondroitin sulphate (OSCS) but also other materials which could potentially be used to counterfeit heparin in the future.
The 2008 case of falsification of heparin with OSCS led to dozens of fatalities around the world, and was made all the more alarming because the contaminated material had passed standard pharmacopoeial quality tests.
In this case the addition of OSCS was a deliberate act to boost limited supplies of heparin with a substance that would fool identity testing. Unfortunately OSCS can also cause serious allergic side effects.
Since then a number of more sensitive methods have been developed to detect OSCS adulteration, but in some respects this could be described as shutting the stable door after the horse has bolted.
“Contamination with OSCS is unlikely to be repeated [but] use of other compounds to counterfeit heparin must be considered,” say the researchers from Christian-Albrechts University in Kiel, Germany.
The team – Susanne Alban, Susanne Lühn and Simone Schiemann – had previously developed a fluorescence microplate assay for detecting OSCS, and have now combined that with a second (anti-Factor Xa) assay. When used together the two tests can identify heparin that is adulterated with a range of different compounds designed to mimic its identity and activity.
The method successfully identified contamination with compounds such as bovine serum albumin (BSA; used to boost apparent protein levels), other heparin mimetics such as pentosan polysulfate and dextran sulfate, and also Factor Xa inhibitors such as rivaroxaban, which could also be used to falsify heparin by boosting its apparent anticoagulant activity.
The authors note that the techniques do not require expensive equipment or specialist knowledge, so are suitable for use as screening tests, for example for “in-process control during production in workshops and consolidation plants or for the initial control of a heparin batch before the comprehensive quality control which nowadays has partly to be commissioned to other laboratories.”
Securing Pharma