TY - JOUR
T1 - Rapid Separation and Quantitation of Cocaine and its Metabolites in Human Serum by Differential Mobility Spectrometry-tandem Mass Spectrometry (DMS-MS-MS)
AU - Dempsey, Sara K.
AU - Moeller, F. Gerard
AU - Poklis, Justin L.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) grants P30DA033934, U54DA03899, and National Institute on Drug Abuse (NIDA) grant T32DA007027-42.
Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press. All rights reserved.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Cocaine continues to be one of the most widespread abused illicit drugs in the USA. Rapid methods are needed for the identification and quantitation of cocaine and its metabolites, benzoylecgonine (BE), ecgonine methyl ester (EME) and cocaethylene (CE), in biological specimens by clinical and forensic toxicology laboratories. Presented is a differential ion mobility spectrometry-tandem mass spectrometry (DMS-MS-MS) method for the analysis of cocaine and its major metabolites in human serum that requires minimal sample preparation and no column chromatography. A Shimadzu Nexera X2 ultra-high performance liquid chromatography system was used to infuse the samples into the DMS cell at a rate of 30 μL/min. Separation of cocaine and its metabolites were performed in a SelexION DMS component from Sciex coupled to a QTRAP 6500 with an IonDrive Turbo V source for TurbolonSpray® using acetonitrile as a chemical modifier. Analysis consisted of ramping the CoV from -35 V to -6 V while monitoring the multiple reaction monitoring (MRM) transitions of each analyte. The assay was evaluated for linearity, bias, precision, carryover, interferences and stability. Calibration curves ranged from 10 to 1,000 ng/mL with linear regression correlation coefficients (r2) of 0.9912 or greater for each analyte. The limit of quantitation was set at 10 ng/mL. Intra-day precision (%CV) ranged from 0% to 15% for cocaine, 1% to 19% for BE, 1% to 17% for EME and 0% to 18% for CE. Inter-day precision ranged from 9% to 14% for cocaine, 2% to 17% for BE, 5% to 11% for EME and 5% to 15% for CE. No carryover or interferences were detected. Bland-Altman analysis of previously analyzed specimens by UPLC-MS-MS showed variability of 30% or less. The method demonstrates the applicability of DMS-MS-MS for high throughout analysis of drugs and their metabolites in clinical and forensic toxicology laboratories.
AB - Cocaine continues to be one of the most widespread abused illicit drugs in the USA. Rapid methods are needed for the identification and quantitation of cocaine and its metabolites, benzoylecgonine (BE), ecgonine methyl ester (EME) and cocaethylene (CE), in biological specimens by clinical and forensic toxicology laboratories. Presented is a differential ion mobility spectrometry-tandem mass spectrometry (DMS-MS-MS) method for the analysis of cocaine and its major metabolites in human serum that requires minimal sample preparation and no column chromatography. A Shimadzu Nexera X2 ultra-high performance liquid chromatography system was used to infuse the samples into the DMS cell at a rate of 30 μL/min. Separation of cocaine and its metabolites were performed in a SelexION DMS component from Sciex coupled to a QTRAP 6500 with an IonDrive Turbo V source for TurbolonSpray® using acetonitrile as a chemical modifier. Analysis consisted of ramping the CoV from -35 V to -6 V while monitoring the multiple reaction monitoring (MRM) transitions of each analyte. The assay was evaluated for linearity, bias, precision, carryover, interferences and stability. Calibration curves ranged from 10 to 1,000 ng/mL with linear regression correlation coefficients (r2) of 0.9912 or greater for each analyte. The limit of quantitation was set at 10 ng/mL. Intra-day precision (%CV) ranged from 0% to 15% for cocaine, 1% to 19% for BE, 1% to 17% for EME and 0% to 18% for CE. Inter-day precision ranged from 9% to 14% for cocaine, 2% to 17% for BE, 5% to 11% for EME and 5% to 15% for CE. No carryover or interferences were detected. Bland-Altman analysis of previously analyzed specimens by UPLC-MS-MS showed variability of 30% or less. The method demonstrates the applicability of DMS-MS-MS for high throughout analysis of drugs and their metabolites in clinical and forensic toxicology laboratories.
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U2 - 10.1093/jat/bky055
DO - 10.1093/jat/bky055
M3 - Article
C2 - 30371848
AN - SCOPUS:85055616772
SN - 0146-4760
VL - 42
SP - 518
EP - 524
JO - Journal of Analytical Toxicology
JF - Journal of Analytical Toxicology
IS - 8
ER -