High-throughput analysis of drugs in biological fluids by desorption electrospray ionization mass spectrometry coupled with thin liquid membrane extraction

TY - JOUR

T1 - High-throughput analysis of drugs in biological fluids by desorption electrospray ionization mass spectrometry coupled with thin liquid membrane extraction

AU - Rosting, Cecilie

AU - Pedersen-Bjergaard, Stig

AU - Hansen, Steen Honore'

AU - Janfelt, Christian

PY - 2013/10/21

Y1 - 2013/10/21

N2 - Biological fluids such as urine, saliva and whole blood were analyzed for contents of drugs by a new combination of desorption electrospray ionization mass spectrometry (DESI-MS) and thin liquid membrane extraction (TLME). Analytes from the sample were extracted into a thin liquid membrane of hexadecane deposited on a porous Teflon membrane, from which they were subsequently analyzed directly by DESI. The total analysis time was 15 minutes for analysis of several samples with a potential analysis time of less than a minute per sample. Thanks to the pre-concentration and sample clean-up built into the method, methadone was detected in urine in full-scan mode with an LOD of 4 ng mL(-1), while amitriptyline, nortriptyline and pethidine showed LODs of 17 ng mL(-1). Quantification was possible for several basic drugs using one common internal standard, providing relative accuracies in the range of 10-30%. A reliability test was performed on 20 samples with methadone, amitriptyline, nortriptyline and pethidine in urine, showing that none of the samples having concentrations above the LOD were missed and no false positives were found. Diphenhydramine and one of its metabolites were detected in authentic samples of urine and saliva, and methadone was detected from a whole-blood sample spiked to a concentration of 100 ng mL(-1). The method has several advantages, such as extremely low price in consumables, the possibility of fast analysis of very crude biofluids such as whole blood and the potential for a very high sample throughput.

AB - Biological fluids such as urine, saliva and whole blood were analyzed for contents of drugs by a new combination of desorption electrospray ionization mass spectrometry (DESI-MS) and thin liquid membrane extraction (TLME). Analytes from the sample were extracted into a thin liquid membrane of hexadecane deposited on a porous Teflon membrane, from which they were subsequently analyzed directly by DESI. The total analysis time was 15 minutes for analysis of several samples with a potential analysis time of less than a minute per sample. Thanks to the pre-concentration and sample clean-up built into the method, methadone was detected in urine in full-scan mode with an LOD of 4 ng mL(-1), while amitriptyline, nortriptyline and pethidine showed LODs of 17 ng mL(-1). Quantification was possible for several basic drugs using one common internal standard, providing relative accuracies in the range of 10-30%. A reliability test was performed on 20 samples with methadone, amitriptyline, nortriptyline and pethidine in urine, showing that none of the samples having concentrations above the LOD were missed and no false positives were found. Diphenhydramine and one of its metabolites were detected in authentic samples of urine and saliva, and methadone was detected from a whole-blood sample spiked to a concentration of 100 ng mL(-1). The method has several advantages, such as extremely low price in consumables, the possibility of fast analysis of very crude biofluids such as whole blood and the potential for a very high sample throughput.

KW - Body Fluids

KW - Chromatography, Liquid

KW - High-Throughput Screening Assays

KW - Humans

KW - Liquid-Liquid Extraction

KW - Pharmaceutical Preparations

KW - Spectrometry, Mass, Electrospray Ionization

KW - Tandem Mass Spectrometry

U2 - 10.1039/C3AN00544E

DO - 10.1039/C3AN00544E

M3 - Journal article

C2 - 23942700

SN - 0003-2654

VL - 138

SP - 5965

EP - 5972

JO - Analyst

JF - Analyst

IS - 20

ER -