Are there traces of BHT and Antioxidant 425 in hospital compounded drug products ?

6 October 2017

C. Fauchère^1,2, M. Berger¹, F. Sadeghipour^1,2 1 Lausanne University Hospitals (CHUV), 46 Bugnon Street, 1011 Lausanne, Switzerland
2 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland

Objective

BHT and Antioxidant 425 are found in pharmaceutical packaging materials (rubber). BHT is hepatotoxic and Antioxidant 425 may affect male fertility. Therefore, we should evaluate the potential of these substances to leach into a drug product. The aim of this study is to screen, identify and quantify BHT and Antioxidant 425 in three pharmaceutical packagings (BD Perfusion® syringe, BD Sterifill® syringe and COC vial, Promens/Elpack®) filled with various solutions including an insulin pediatrics solution.

Method

The pharmaceutical packagings are filled with 1 UI/mL insulin solution as well as with isopropanol/water 50 :50 mixture and with two phosphate buffers (pH 3 and 8) to assess if traces of BHT and Antioxidant 425 could be found under extreme conditions. BHT and Antioxidant 425 are extracted by Solid Phase Extraction (SPE) and analyzed by a validated HPLC/DAD method (according to SFSTP protocol).

Results

No detectable trace of BHT is found in tested samples. Antioxidant 425 is only found in solutions stored in BD Perfusion® syringe, sometimes at high level (> 40 µg/mL in isopropanol/water 50:50 mixture). The estimated dose of Antioxidant 425 received by a patient is below the toxicity threshold.

Discussion/conclusion
It would be better to use COC vials or BD Sterifill® syringes for long term storage of hospital compounded drug products in which no traces of BHT and Antioxidant 425 are found. For safety reasons, a study should be designed to identify all other leachable substances which migrated into the drug product.