Measurement of propofol concentration in sheep blood and plasma: Effect of storage at different temperatures

doi:10.1016/1056-8719(95)00094-1

Journal of Pharmacological and Toxicological Methods

Volume 34, Issue 4, December 1995, Pages 199-202

https://doi.org/10.1016/1056-8719(95)00094-1 Get rights and content

Abstract

In planning a study of the pharmacokinetics of propofol in sheep, contradictions were noted in the literature with regard to loss of propofol during storage of blood samples. This prompted a study of such loss from samples of sheep blood and plasma during storage at room temperature, +4° C and −20° C, for up to 17 days, over a range of concentrations from 1 to 20 μg/mL. Samples were drawn from 22 different sheep. Analysis was by the method of Adam et al. (1981). The best estimate of the overall mean loss rate was 0.7% per day with 95% confidence limits of 0.3% to 1.2% per day. The loss rate increased nonsignificantly with storage temperature. There were very small nonsignificant differences of loss rate between plasma and blood, between different concentrations, and between genders. There were significant differences of loss rate between sheep—up to about 2% per day in blood or plasma from any one sheep.

References (5)

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Estimation of ICI 35,868 (Diprivan) in blood by high-performange liquid chromatography, following coupling with Gibbs' reagent
J Chromatogr
(1981)
GF Plummer
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J Chromatogr
(1987)

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Cited by (6)

Tissue/blood and tissue/water partition coefficients for propofol in sheep
2001, British Journal of Anaesthesia
Citation Excerpt :
This was done to provide information on possible loss by continuing metabolism of propofol in the liver before freezing. Analysis of propofol in blood samples was as described previously2 with derivatizations4 of two 1-ml subsamples, each analysed in duplicate. For analysis of propofol in tissue, a subsample of each frozen tissue sample was taken by grating and the remainder returned to the freezer.
The primary objective of this study was to determine in vivo tissue/blood partition coefficients of propofol for use in physiological modelling of its pharmacokinetics. The sheep was used as an animal model. In the main series of experiments, crossbred ewes received a bolus of propofol 1% (Diprivan) followed by an infusion during which blood concentrations were measured at intervals. After 2 h, the sheep were killed with an injection of potassium chloride, and tissue samples were taken for storage at –20°C and subsequent analysis. Tissue/blood partition coefficients depend on the amount of triglyceride which accumulates in blood from the propofol vehicle; for blood, free of added triglyceride, the following coefficients were calculated: brain, 3.23; heart, 5.94; kidney, 2.46; spleen, 1.86; semimembranosus muscle, ≥1.61; triceps muscle, ≥1.47. Calculated tissue/water coefficients were 35 times greater. There was indirect evidence of extraction of propofol by the lungs.
Propofol anesthesia
1999, Veterinary Clinics of North America - Small Animal Practice
Although questions may still remain regarding the use of this unique sedative-hypnotic drug with anesthetic properties in highrisk patients, these studies have provided cardiopulmonary and neurologic evidence of the efficacy and safety of propofol when used as an anesthetic under normal and impaired conditions in the dog. In nonpremedicated dogs, the quality of induction, anesthesia, and recovery following propofol is desirable. Muscle relaxation and the degree of analgesia observed with propofol alone are suitable for minor diagnostic procedures. The patient is bright and alert within a few minutes after propofol anesthesia with excellent psychomotor function. The use of potent sedative/analgesics or analgesics enhances the degree of muscle relaxation and analgesia desirable for surgical procedures. These studies have shown propofol to be an anesthetic that can be employed in a wide range of research and clinical conditions.
Partitioning of propofol between blood cells, plasma and deproteinised plasma in sheep
1998, Veterinary Anaesthesia and Analgesia
The partitioning of propofol within the blood, when administered in its usual emulsion carrier, has been determined in vitro in sheep. The blood:plasma ratio was found to be 1.13 and the blood-cell:plasma ratio 1.42. When oxalate was used as the anticoagulant, the plasma protein binding was calculated to be 92.6% - slightly lower than reported for dog, rat, rabbit and man. However, when heparin was the anticoagulant, the binding was significantly less, 83.0%. Differences from some results in the literature may be attributable to other workers using propofol without the lipid emulsion carrier. From the results of this study it is argued that anaemia and plasma levels of protein and lipid may affect propofol requirements.
Comparison of arterialized venous with arterial blood propofol concentrations during sub-anaesthetic infusions in volunteers
1996, British Journal of Anaesthesia
We have compared propofol concentrations in arterial and arterialized venous blood (from the radial artery at the wrist and a vein in the opposite forearm) in five volunteers during a sub-anaesthetic increasing infusion regimen designed to produce pseudo-steady-state arterial concentrations of 0.06, 0.17 and 0.43 micrograms ml-1. As in a previous study, we found no statistically significant difference between sampling sites (P = 0.66). However, changes in the method of arterialization yielded a reduction in the observed variability, with the arterialized venous propofol concentration lying within +/- 23% (95% reference interval) of the corresponding arterial concentration compared with 1 +/- 43%, as reported previously.
The anesthetic interaction of propofol and sevoflurane on the minimum alveolar concentration preventing motor movement (MAC<inf>NM</inf>) in dogs
2015, Canadian Journal of Veterinary Research
Propofol hydroxylation by dog liver microsomes: Assay development and dog breed differences
1999, Drug Metabolism and Disposition

^☆: This work was carried out in the Wellcome Comparative Anaesthetic Laboratory, which was provided by the Wellcome Trust, and the research was generously funded by the Perry Foundation.

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Original articleMeasurement of propofol concentration in sheep blood and plasma: Effect of storage at different temperatures☆

Abstract

J Chromatogr

J Chromatogr

Original article
Measurement of propofol concentration in sheep blood and plasma: Effect of storage at different temperatures☆