Determination of Barbiturates in Biological Specimens by Flat Membrane-Based Liquid-Phase Microextraction and Liquid Chromatography-Mass Spectrometry

Abstract

The wide abuse of barbiturates has aroused extensive public concern. Therefore, the determination of such drugs is becoming essential in therapeutic drug monitoring and forensic science. Herein, a simple, efficient, and inexpensive sample preparation technique, namely, flat membrane-based liquid-phase microextraction (FM-LPME) followed by liquid chromatography-mass spectrometry (LC-MS), was used to determine barbiturates in biological specimens. Factors that may influence the efficiency including organic extraction solvent, pH, and composition of donor and acceptor phases, extraction time, and salt addition to the sample (donor phase) were investigated and optimized. Under the optimized extraction conditions, the linear ranges of the proposed FM-LPME/LC-MS method (with correlation coefficient factors ≥ 0.99) were 7.5–750 ng mL−1 for whole blood, 5.0–500 ng mL−1 for urine, and 25–2500 ng g−1 for liver. Repeatability between 5.0 and 13.7% was obtained and the limit of detection (LOD) values ranged from 1.5 to 3.1 ng mL−1, from 0.6 to 3.6 ng mL−1, and from 5.2 to 10.0 ng g−1 for whole blood, urine, and liver samples, respectively. This method was successfully applied for the analysis of barbiturates in blood and liver from rats treated with these drugs, and excellent sample cleanup was achieved.

Keywords

• membrane-based microextraction
• barbiturates
• simultaneous determination
• whole blood
• urine
• liver