Journal article
Assessment of the Stability of Supraphysiological Ascorbate in Human Blood: Appropriate Handling of Samples from Clinical Trials for Measurements of Pharmacological Ascorbate
Radiation research, Vol.191(6), pp.491-496
06/2019
DOI: 10.1667/RR15328.1
PMCID: PMC6608566
PMID: 31039080
Abstract
Based on encouraging results from several early-phase clinical trials, there is renewed interest in the use of pharmacological ascorbate (i.e., intravenous administration resulting in >≈10 m
plasma ascorbate concentrations) in combination with standard-of-care cancer treatments including radiation and/or chemotherapy. Under normal, healthy physiological conditions, humans maintain plasma ascorbate concentrations in the range of 40-80 l
. However,
antitumor activity requires supraphysiological plasma concentrations on the order of ≈20 m
. The stability of ascorbate in whole blood has been well studied. The goal of this work was to determine the appropriate handling methods of blood samples, after treatment with pharmacological ascorbate, which allow for the optimal measurement of ascorbate in plasma for dosing verification. Our findings indicate that ascorbate concentrations (m
) are relatively stable in whole blood collected in sodium heparin tubes and stored on ice (or at 4°C) for up to 24 h. After 24 h, ascorbate levels in plasma are relatively stable at 4°C for up to 72 h. At -20°C, plasma concentrations are relatively stable for 2-3 weeks, while at -80°C, ascorbate concentrations in plasma are stable for at least one month. In contrast, patient samples showed better stability when stored as whole blood compared to plasma at 4°C but increasing hemolysis over time may significantly skew ascorbate measurements. Additionally, patient samples can be reliably stored as plasma at -20°C for up to three weeks in either a frost-containing or frost-free environment. This information can guide the collection, processing and storage of clinical samples after pharmacological ascorbate infusions amenable to multi-center clinical trials.
Details
- Title: Subtitle
- Assessment of the Stability of Supraphysiological Ascorbate in Human Blood: Appropriate Handling of Samples from Clinical Trials for Measurements of Pharmacological Ascorbate
- Creators
- Michael S Petronek - a Free Radical and Radiation Biology Program, Department of Radiation OncologyBrett A Wagner - a Free Radical and Radiation Biology Program, Department of Radiation OncologyNancy J Hollenbeck - a Free Radical and Radiation Biology Program, Department of Radiation OncologyJoseph M Caster - b Holden Comprehensive Cancer Center and Department of SurgeryDouglas R Spitz - b Holden Comprehensive Cancer Center and Department of SurgeryJoseph J Cullen - d Veterans Affairs Medical Center, Iowa City, IowaGarry R Buettner - b Holden Comprehensive Cancer Center and Department of SurgeryBryan G Allen - b Holden Comprehensive Cancer Center and Department of Surgery
- Resource Type
- Journal article
- Publication Details
- Radiation research, Vol.191(6), pp.491-496
- DOI
- 10.1667/RR15328.1
- PMID
- 31039080
- PMCID
- PMC6608566
- NLM abbreviation
- Radiat Res
- ISSN
- 0033-7587
- eISSN
- 1938-5404
- Publisher
- United States
- Grant note
- R01 CA184051 / NCI NIH HHS R01 CA182804 / NCI NIH HHS P01 CA217797 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS
- Language
- English
- Date published
- 06/2019
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Surgery; Radiation Oncology
- Record Identifier
- 9984046834002771
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