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The authors evaluated an analyser for the determination of propofol concentrations in whole blood. The Pelorus 1000 (Sphere Medical) measures propofol concentrations in around 5 min without the requirement for sample preparation. The performance of the analyser was characterised with respect to linearity, precision in control solutions and whole blood and method comparison to an HPLC based reference method. In addition, the effects of substances considered to potentially affect the assay method were investigated. The analyser was found to be linear up to 12 μg/ml (R2 = 0.9993), with a lower limit of quantification of 0.75 μg/ml. Total within device imprecision in control solutions was 0.11 μg/ml at 5.32 μg/ml and 0.17 μg/ml at 10.3 μg/ml. Within run precision in whole blood was 0.04 μg/ml at 2.84 μg/ml and 0.08 μg/ml at 6.68 μg/ml and for the reference method was 0.06 μg/ml and 0.12 μg/ml respectively. In comparison to the reference method, the overall bias of the Pelorus 1000 system over the range is estimated to be 0.15 μg/ml (95% confidence interval -0.11-0.41 μg/ml). The only cross interference of note is to a highly elevated level of conjugated bilirubin, while low haematocrit levels lead to a 0.13 μg/ml under reading with respect to the HPLC reference. The system fulfils the requirements for measurement of propofol concentrations in whole blood samples with precision and accuracy suitable for elucidating propofol pharmacokinetics at clinically relevant concentrations. With no requirement for sample preparation and a fast time to results, the analyser opens up the possibility of studies to measure and respond to blood propofol concentrations in patients in close to real time.

SummaryWe report laboratory and clinical evaluations of a blood propofol concentration analyser. Laboratory experiments used volunteer blood spiked with known propofol concentrations over the clinically relevant concentrations from 0.5 to 16 lg.ml )1 to assess linearity and the influence of haematocrit and concurrent drug administration. Analyser concentrations demonstrated excellent linearity (R 2 = 0.999). Blood spiked with commonly used drugs showed no significant variation compared to unspiked controls. Propofol measurements were largely independent of haemoglobin concentration. A 6% decay in propofol concentration was observed at the highest prepared concentration. Clinical performance of the analyser was assessed using 80 arterial blood samples from 72 patients receiving propofol infusions during cardiac surgery. Samples were processed using the propofol analyser, and high performance liquid chromatography (HPLC) used as a gold-standard comparator. These data demonstrated excellent agreement between the propofol analyser and HPLC with a bias of 0.13 lg.ml )1 and precision of )0.16 to 0.42 lg.ml Target-controlled infusion (TCI) is a common method of propofol administration. The ability of TCI algorithms to predict blood propofol concentrations accurately is poor [1, 2], with measures of precision demonstrating errors of up to 60% [3]. Significant bias and large errors in precision are also identified in groups falling outside of limits used in the development of these algorithms [4][5][6]. Conventional methods of measuring propofol concentrations in blood include high performance liquid chromatography (HPLC), gas chromatography and liquid chromatography mass spectroscopy. These are labour intensive and time consuming methods and cannot be used to deliver clinically useful information. Estimation of blood propofol from expired gases has yet to demonstrate consistent and reliable results [7].We assessed a device designed to measure the concentration of propofol in a blood sample in 4 min by extracting propofol from 0.5 ml of whole blood using solid phase extraction and quantifying the amount of propofol in the extract using colorimetric detection techniques. This technique for propofol extraction was first described in 2006 in a proof of concept study [8]. We conducted both laboratory and clinical evaluations of the device, the latter using samples from patients undergoing propofol-based general anaesthesia for cardiac surgery.

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