Determination of Propofol in Biological Samples

Importance of Topic

Accurate determination of propofol levels in biological samples is essential for both clinical monitoring and forensic investigations. Propofol’s rapid distribution and clearance, combined with its common use as an anesthetic agent, demand sensitive, selective methods that can reliably quantify low concentrations in complex matrices such as blood, serum, urine, and tissue homogenates. This capability supports patient safety, toxicological assessments, and legal casework.

Objectives and Study Overview

This application note describes the development and validation of a GC–quadrupole ion trap MS/MS method for identifying and quantifying propofol in various biological specimens. The method employs an isotopically labeled internal standard (propofol-d17) and aims to demonstrate linearity, sensitivity, and robustness over a working range of 0.1–2.0 µg/mL.

Used Methodology and Instrumentation

Sample Preparation:

• Alkalinize 1 mL of sample with carbonate/bicarbonate buffer (pH 11).
• Add propofol-d17 internal standard and extract with heptane.
• Vortex, rotate, and centrifuge to separate layers.
• Transfer 200 µL of organic phase into GC vials for analysis.

Used Instrumentation

Gas Chromatograph–Ion Trap Mass Spectrometer Configuration:

• GC Column: 25 m × 0.20 mm × 0.33 µm DB-5ms Ultra Inert or equivalent.
• Injection: 2 µL splitless at 250 °C.
• Carrier Gas: Helium at 1.3 mL/min.
• Oven Program: 70 °C (1 min), ramp 25 °C/min to 310 °C (4.4 min hold).
• MS Mode: EI-MS/MS scan (60–180 Da) with auto-tune; source temps: trap 210 °C, manifold 50 °C, transfer line 310 °C.

Main Results and Discussion

The calibration curve demonstrated excellent linearity (R² = 0.9994) across 0.1–2.0 µg/mL. The method limit of detection was 0.05 µg/mL, and the limit of quantitation was 0.10 µg/mL. Chromatographic peaks for propofol and propofol-d17 showed consistent retention times within ±2% of calibrators. Ion ratios for quantitation and qualification met acceptance criteria, and no significant carryover or matrix interferences were observed.

Benefits and Practical Applications

This GC-QIT MS/MS approach offers:

• High selectivity and sensitivity, reducing false positives and negatives.
• Improved signal-to-noise ratio and minimized matrix effects.
• Applicability to multiple biological matrices with a simple, reproducible extraction.
• Rapid throughput suitable for forensic and clinical laboratories.

Future Trends and Potential Applications

Emerging directions to enhance propofol analysis include:

• Integration of high-resolution and ambient ionization techniques.
• Automation and microextraction to reduce sample volumes and hands-on time.
• Multi-analyte panels combining propofol with other anesthetics or metabolites.
• Point-of-care devices leveraging miniaturized GC–MS systems for bedside monitoring.

Conclusion

The described GC–quadrupole ion trap MS/MS method delivers a fast, targeted, and reliable protocol for propofol determination in diverse biological specimens. Its excellent sensitivity, linearity, and robustness make it well suited for routine forensic and clinical toxicology applications.

Reference

1. Baselt RC, Cravey RH. Disposition of Toxic Drugs and Chemicals in Man, 7th Ed., 2014, pp. 949–951.
2. Hikiji W et al. Simple and Sensitive Method for the Determination of Propofol in Human Solid Tissues by GC–MS. J Anal Toxicol. 2010, Vol. 34.