Highly Sensitive CE-ESI-MS/MS for Accurate Quantitation of Drugs of Abuse in Bioanalysis Using the Agilent 6490 Triple Quadrupole LC/MS System

The combination of capillary electrophoresis and mass spectrometry (CE-MS) is particularly well suited to forensic toxicology due to its high separation efficiency, selectivity and sensitivity, short analytical time, and low solvent and sample consumption. A CE-ESI-MS/MS method was developed for the quantitation of drugs of abuse in urine samples with the highly sensitive Agilent 6490 Triple Quadrupole LC/MS system, including Jet Stream and ion funnel technologies, equipped with a triple-tube sprayer especially designed for CE hyphenation. Urines were simply diluted 10-fold prior to CE injection, and a pH-mediated stacking procedure was implemented to increase the loading capacity (20.5 % of the capillary length). This approach was found to increase the sensitivity of the method with limits of detection (LODs) as low as the ng/mL level. The quantitative analytical procedure was validated for two model compounds, cocaine (COC) and methadone (MTD), according to SFSTP protocols and guidance of the Food and Drug Administration (FDA). Performance was evaluated for selectivity, response function, the limit of quantitation (LOQ), trueness, precision, and accuracy. COC was fully validated over a concentration range of 10–1,000 ng/mL, with accuracy included within the ± 30 % tolerance limits, as for MTD in the concentrations range of 21–1,000 ng/mL. The developed CE-ESI-MS/MS was eventually applied to real cases analysis.