Application of a benchtop colorimetric method for quantification of blood propofol levels

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ORIGINAL RESEARCH

Application of a benchtop colorimetric method for quantification of blood propofol levels Logan J. Voss1 · John C. Voss1 · Jamie W. Sleigh2 Received: 16 July 2020 / Accepted: 29 October 2020 © Springer Nature B.V. 2020

Abstract Quantification of plasma propofol (2,6-diisopropylphenol) in the context of clinical anaesthesia is challenging because of the need for offline blood sample processing using specialised laboratory equipment and techniques. In this study we sought to refine a simple procedure using solid phase extraction and colorimetric analysis into a benchtop protocol for accurate blood propofol measurement. The colorimetric method based on the reaction of phenols (e.g. propofol) with Gibbs reagent was first tested in 10% methanol samples (n = 50) containing 0.5–6.0 µg/mL propofol. Subsequently, whole blood samples (n = 15) were spiked to known propofol concentrations and processed using reverse phase solid phase extraction (SPE) and colorimetric analysis. The standard deviation of the difference between known and measured propofol concentrations in the methanol samples was 0.11 µg/mL, with limits of agreement of − 0.21 to 0.22 µg/mL. For the blood-processed samples, the standard deviation of the difference between known and measured propofol concentrations was 0.09 µg/mL, with limits of agreement − 0.18 to 0.17 µg/mL. Quantification of plasma propofol with an error of less than 0.2 µg/mL is achievable with a simple and inexpensive benchtop method. Keywords  Anaesthesia · Propofol · Measurement · Colorimetric

1 Introduction Propofol (2,6-diisopropylphenol) is a central nervous system depressant that is widely used for induction and maintenance of general anaesthesia. When used for anaesthesia maintenance, intravenous delivery of propofol is controlled by infusion pumps programmed with pharmacokinetic models that estimate the plasma propofol concentration. A serious drawback of these “target controlled infusion” devices is the inherent inaccuracies in the population-based models that drive them [1]. Direct measurement of plasma propofol can be achieved with high levels of accuracy using mass spectrometric [2] and high-performance liquid chromatographic [3] methods. However, these techniques require specialised equipment and laboratory expertise that are not readily accessible to * Logan J. Voss [email protected] 1



Anaesthesia Department, Waikato District Health Board, Pembroke St, Hamilton, New Zealand



Department of Anesthesia, Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand

2

most anaesthetic departments. For this reason, in 2006 we developed an automated device, based on solid phase extraction (SPE) and colorimetric analysis, which showed promise as a simple, inexpensive method for rapid, accurate quantification of plasma propofol levels [4]. This SPE-based device was commercialised as the Pelorus 1000 (Sphere Medical) [5], but is no longer available. Solid phase extraction is a sample preparation technique that concentrates and extracts