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Storage of nitroglycerin (NTG) admixed with HBOC-201 for 30 days in polyolefin plastic bags: a pilot study

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Abstract

Hemorrhaged animals have benefited from resuscitation with the hemoglobin-based oxygen carrier (HBOC-201). Co-infusion of nitric oxide (NO) via separate intravascular lines is effective in attenuating HBOC-induced elevation of blood pressure. We tested whether nitroglycerin (NTG) and HBOC-201 can be packaged together as a single drug for resuscitation. Since NTG binds easily to plastics such as polyvinylchloride, we assessed the stability of this combination in oxygen barrier double-layer ethylene-vinyl alcohol/polyolefin bags over a 30-day period. Outcome measures indicative of the stability of HBOC/NTG were reported as changes in levels of hemoglobin (Hb), methemoglobin (MetHb), NTG, and nitrite over time. Individual tightly sealed small aliquots of HBOC/NTG were prepared under nitrogen and analyzed in a timely fashion from 0 to 30 days using hematology instruments, HPLC, FPLC, and chemiluminescence. The level of NTG in the HBOC/NTG mixture was reduced significantly over time whereas it was stable in control mixtures of NTG/saline. The level of total Hb in the HBOC/NTG and HBOC/saline mixtures remained stable over time. MetHb formed and increased to 6% up to day 1 and then slowly decreased in the HBOC/NTG mixture whereas it remained unchanged in the HBOC/saline mixture. Nitrite was produced in the HBOC/NTG group upon mixing, was increased at day 1, and then became undetectable. The reaction between HBOC-201 and NTG occurring upon mixing and developing over time in polyolefin bags makes the long-term storage of this mixed combination inappropriate.

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Acknowledgements

The authors would like to thank Michael Hammett and Roli Pessu for technical assistance processing the samples and Tatyana Belinskaya (MSc) for her assistance with chromatography. We thank Drs. Paula Moon-Massat and Charles Auker for revising and editing this manuscript.

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Authors and Affiliations

  1. Naval Medical Research Center(NMRC), Operational and Undersea Medicine, NeuroTrauma Department, 503 Robert Grant Ave, Silver Spring, MD, 20910-7500, USA

    Savita Nigam, Richard McCarron & Francoise Arnaud

  2. Combat Casualty Care Research Program, USAMRMC, Fort Detrick, MD, 21702, USA

    Savita Nigam

  3. Department of Surgery, USUHS, Bethesda, MD, 20814, USA

    Richard McCarron & Francoise Arnaud

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  1. Savita Nigam
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  2. Richard McCarron
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Contributions

F.A: designed the study, performed data acquisition, compilation, analysis and interpretation of data, wrote manuscript.

S.V: designed the study, performed laboratory and chromatography assays, collection and analysis of data, wrote manuscript.

R.M: revised and edited the manuscript.

Corresponding author

Correspondence to Francoise Arnaud.

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Disclosure

This work was funded by work unit number 604771N.9737.001.A0315. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government. I am a military service member (or employee of the US Government). This work was prepared as part of official duties. Title 17 U.S.C. § 105 provides that “Copyright protection under this title is not available for any work of the US Government.” Title 17 U.S.C. § IOI defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties.

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The authors declare that they have no conflict of interest.

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Nigam, S., McCarron, R. & Arnaud, F. Storage of nitroglycerin (NTG) admixed with HBOC-201 for 30 days in polyolefin plastic bags: a pilot study. Drug Deliv. and Transl. Res. 7, 674–682 (2017). https://doi.org/10.1007/s13346-017-0411-6

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  • DOI: https://doi.org/10.1007/s13346-017-0411-6

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