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

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.

Low-Temperature Plasma Probe Mass Spectrometry for Analytes Separated on Thin-Layer Chromatography Plates: Direct vs Laser Assisted Desorption

“…For example, the LOD of propofol was determined to be 0.77 ng/mm 2 , which is equivalent to 3.7 μg mL –1 if the volume of standard solution spotted on the TLC plate (2 μL) is taken into account, while the therapeutic dose of propofol is 6–10 μg mL –1 for induction of anesthesia . While high uncertainty may result from the LOD being close to the application’s low end range requirements, fast and simple preconcentration methods, recently demonstrated for propofol, are readily available. , Also, the LOD for nicotine was determined as 0.20 ng/mm 2 (∼1.9 ng per sample spot), which shows better performance than the reported LOD of 2 μg for determination of nicotine in cigarettes by the SPME/GC-MS method . On the other hand, when using NP-TLC plates coupled with the LTP-MS system, some analytes cannot be quantified due to no or insufficient analytical response.…”

Dynamic headspace solid-phase extraction at room temperature: a theoretical model, method, and application for propofol analysis

“…To date, many analytical techniques such as liquid chromatography-mass spectroscopy (LC-MS), 19,20 gas chromatography-mass spectrometry (GC-MS), 21,22 ion mobility spectrometry (IMS), 23–25 electrochemical 26 and electrochemiluminescence 27 have been successfully used for propofol analysis. Results revealed that the proposed method leads to higher extraction efficiency and sensitivities for the quantification of trace PF serum sample matrices, while it can also overcome some limitations of conventional HS.…”

Cerebrospinal fluid penetration of targeted therapeutics in pediatric brain tumor patients

“…Recent studies have shown the importance of the determination of free levels for CNS drugs [4,17,25,27,28]. However, the analytical access to free levels is generally associated with considerable expenditure on equipment [29,30], especially in CSF, where the total concentrations of drugs are significantly lower compared to serum [25,31]. As protein levels in CSF are multiple orders of magnitude lower than in serum, protein binding is therefore usually neglected in CSF.…”