Eight commonly used sulfonylureas (SUs:  nicosulfuron, thifensulfuron methyl, metsulfuron methyl, sulfometuron methyl, chlorsulfuron, bensulfuron methyl, tribenuron methyl, and chlorimuron methyl) and deuterium-labeled nicosulfuron (nicosulfuron-d(6)), used as an internal standard, were isolated from soil by solvent extraction and identified under quantitative and qualitative ion spray LC/MS/MS conditions using the selected reaction monitoring (SRM) mode of acquisition. The lower level of quantitation for these SUs in soil was determined at the 0.05 ppb level using a TurboIonSpray adapted LC/MS interface without a precolumn split and optimizing MS/MS tuning conditions for individual SUs. The eight SUs were qualitatively identified and quantitatively determined in soil. The standard curve for each SU was linear from 0.05 to 10 ppb. This SRM LC/MS method demonstrates high sensitivity and high specificity for these SUs in soil and shows at least a 400-fold improvement in sensitivity over previous reports. Acceptance criteria for forensically valid data are suggested for qualitative SRM LC/MS experiments. These include HPLC retention time reproducibility (±2%), at least two and preferably three precursor-product ions selected, and relative abundance criteria for selected ions (±20% absolute).

High-throughput parallel synthesis of library compounds for early drug discovery requires high-throughput analytical methods to confirm synthesis, identify reaction products, and determine purity. An ultrafast 1.0-min HPLC/UV/ELSD/MS method was developed and compared to our standard 2.5- and 5.0-min methods in order to determine if the faster method was appropriate to evaluate compound synthesis and determine purity. In addition to using standard test mixtures, a 400-member library produced by high-throughput parallel synthesis was used for comparing the various methods. Mass spectrometric detection was used for compound identification, while UV and ELSD data offered purity assessment. Compared to our longer separations, chromatographic separation achieved using the 1.0-min method was sufficient for compound evaluation and purity assessment. This ultrafast 1.0-min HPLC/UV/ELSD/MS method is expected to increase analytical throughput tremendously, provide important information faster, and reduce the overall cycle time from synthesis to screening.

A sensitive and specific high-performance liquid chromatographic/ionspray tandem mass spectrometric (LC/ionspray MS/MS) method was developed and validated to quantitate leukotriene E4 (LTE4) in human urine. This method involves solid-phase extraction with Empore membrane disks to isolate LTE4 and its internal standard, LTE4-d3, from the urine stabilized with antioxidant and metal ion chelating agent. The reconstituted extracts were analyzed by LC/ionspray MS/MS in the selected reaction monitoring (SRM) mode. The assay has a lower level of quantitation (LOQ) of 50 pg ml-1 for LTE4 based on 5 ml aliquots of urine. The calibration graphs were linear from 50 pg ml-1 to 10 ng ml-1 for LTE4 extracted from urine. The inter- and intra-assay precision (RSD) and accuracy (DEV) did not exceed 11% and 8% at any level of the calibration standards and quality control (QC) samples, respectively. The recovery of LTE4 using the Empore disk solid-phase extraction technology was independent of LTE4 concentration in human urine. The overall extraction recovery for LTE4 was 72% (RSD = 2.14%).

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