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Adsorption and Leachable Contamination of Flucloxacillin, Cyclosporin and Amiodarone Following Delivery Through an Intravenous Administration Set

Abstract

Purpose

Interactions between a pharmaceutical drug and its delivery device can result in changes in drug concentration and leachable contamination. Flucloxacillin, amiodarone and cyclosporin were investigated for drug concentration changes and leachable contamination after delivery through an intravenous administration set.

Methods

Flucloxacillin, amiodarone and cyclosporin were delivered through an intravenous administration set and the eluate analysed by HPLC-UV and HPLC-MS.

Results

The average recovery of flucloxacillin was 99.7% and no leachable compounds were identified. The average recovery of cyclosporin was 96.1%, which contrasts previous findings that have reported up to 50% loss of cyclosporin. This is likely due to the use of DEHP-free administration sets in this study, as adsorption of cyclosporin is linearly related to DEHP content. The average recovery of amiodarone was 91.5%. 5-hydroxymethylfurfural was identified in the amiodarone solution following delivery through the administration set as well as the 5% glucose solution used for delivery.

Conclusions

Drug/administration set interactions may modify pharmaceuticals during delivery. In this study, only 90% of the amiodarone was delivered through a generic administration set. Given the growing use of generic administration sets in hospital settings, validation of the suitability of their use is required to ensure patient safety and expected levels of efficacy.

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Abbreviations

ACN:

Acetonitrile

API:

Active pharmaceutical ingredient

DEHP:

Diethylhexyl phthalate

EMA:

European Medicines Authority

FDA:

Food and Drug Administration

HPLC:

High-performance liquid chromatography

ICH:

International Council for Harmonisation

IV:

Intravenous

LC-MS:

Liquid chromatography-mass spectroscopy

MP A:

Mobile phase A

MP B:

Mobile phase B

PVC:

Poly(vinyl chloride)

UV:

Ultraviolet

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ACKNOWLEDGMENTS AND DISCLOSURES

This research was funded by The Faculty of Science, Health, Engineering and Education, University of the Sunshine Coast. The authors would like to thank Linda Pappalardo for conducting the 5-hydroxymethylfurfural analysis, Ms. Jenny Johns and Prof. Peter Parsons for completing the LC-MS analysis and the clinical staff at the Nambour General Hospital for their expert clinical advice.

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Correspondence to Steven M. Ogbourne.

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Woodward, Z., Brooks, P., Morris-Smith, B. et al. Adsorption and Leachable Contamination of Flucloxacillin, Cyclosporin and Amiodarone Following Delivery Through an Intravenous Administration Set. Pharm Res 35, 121 (2018). https://doi.org/10.1007/s11095-018-2409-2

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KEY WORDS

  • active pharmaceutical ingredient
  • adsorption
  • drug delivery
  • drug product
  • intravenous