Development of a highly sensitive gas chromatography-mass spectrometry method preceded by solid-phase microextraction for the analysis of propofol in low-volume cerebral microdialysate samples.

Armin Sebastian Guntner,Udo Illievich,Michael Kneidinger,Wolfgang Buchberger,Simon Stöcklegger

doi:10.1002/jssc.201801066

Abstract

To date, the commonly used intravenous anesthetic propofol has been widely studied, and fundamental pharmacodynamic and pharmacokinetic characteristics of the drug are known. However, propofol has not yet been quantified in vivo in the target organ, the human brain. Here, cerebral microdialysis offers the unique opportunity to sample propofol in the living human organism. Therefore, a highly sensitive analytical method for propofol quantitation in small sample volumes of 30 μL, based on direct immersion solid‐phase microextraction was developed. Preconcentration was followed by gas chromatographic separation and mass spectrometric detection of the compound. This optimized method provided a linear range between the lower limit of detection (50 ng/L) and 200 μg/L. Matrix‐matched calibration was used to compensate recovery issues. A precision of 2.7% relative standard deviation between five consecutive measurements and an interday precision of 6.4% relative standard deviation could be achieved. Furthermore, the permeability of propofol through a cerebral microdialysate system was tested. In summary, the developed method to analyze cerebral microdialysate samples, allows the in vivo quantitation of propofol in the living human brain. Additionally the calculation of extracellular fluid levels is enabled since the recovery of the cerebral microdialysis regarding propofol was determined.

Highlights

Propofol (2,6-diisopropyl-phenol) is a commonly used intravenous anesthetic agent for inducing and maintaining general anesthesia and/or sedation in intensive care
Propofol as a part of total intravenous anesthesia is applied in target-controlled infusions, which became available in the late 1990s [5]
Stock solutions of propofol were prepared in methanol with a concentration of 2 g/L and stored at 4◦C

Summary

Introduction

Propofol (2,6-diisopropyl-phenol) is a commonly used intravenous anesthetic agent for inducing and maintaining general anesthesia and/or sedation in intensive care. It provides a quick effect (already after 30 s) and rapid recovery of the patient due to its lack of accumulation [1,2]. Propofol as a part of total intravenous anesthesia is applied in target-controlled infusions, which became available in the late 1990s [5].

Methods

Results

Conclusion