Determination of a Sulfur-Containing Drug in Human Plasma by an Improved Method for Sulfur Chemiluminescence Detection in Combination with Capillary Gas Chromatography

An improved method for sulfur chemiluminescence detection in combination with capillary gas chromatography was established. The method was applied to the analysis of a sulfur-containing antiasthma drug, S-1452, and its nine metabolities in human plasma. The high selectivity and sensitivity of the method allowed accurate quantitation of trace levels of these compounds in human plasma with no interferences from the biological components present. To enable stable measurements and maintain reproducibility over a long period, the performance characteristics of a commercially available instrument were investigated. The gas seal in the injection port was found to easily corrode through interaction of the sulfur analyte with the metal gas seal. To prevent this, a disk made from an alloy of platinum and gold (60:40) was mounted on the gas seal. The reproducibility of the measurement was improved remarkably by using the disk. The use of compressed air of high purity significantly lowered the signal-to-noise ratio. The optical filter was kept clean by using a nickel catalyst to trap ozone in place of copper manganese oxide (CuMn2O4). These improvements raised the sensitivity and selectivity with the lower quantitation limits of 0.5-1.0 ng/mL in human plasma.