Novel Selectivity-Based Forensic Toxicological Validation of a Paper Spray Mass Spectrometry Method for the Quantitative Determination of Eight Amphetamines in Whole Blood.

Paper spray tandem mass spectrometry is used to identify and quantify eight individual amphetamines in whole blood in 1.3 min. The method has been optimized and fully validated according to forensic toxicology guidelines, for the quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), and 4-fluoroamphetamine (4-FA).

Transferring Ions from Solution to the Gas Phase: The Two Basic Principles.

The efficient formation of gaseous ions is the crucial step in all successful mass spectrometric experiments. The invention of electrospray ionization (ESI) has strongly facilitated this step by transferring preformed ions directly from solution to the gas phase - thereby circumventing the need to first convert analytes to the gas phase and then ionize them - and therefore ESI has become an extremely useful and widely applied MS technique. The invention of sonic spray ionization (SSI) has also allowed for the transfer of ions from solution into the gas phase, but without the assistance of a voltage or heating.

Forensic Chemistry and Ambient Mass Spectrometry: A Perfect Couple Destined for a Happy Marriage?

Ambient mass spectrometry has been demonstrated, via various proof-of-concept studies, to offer a powerful, rather universal, simple, fast, nondestructive, and robust tool in forensic chemistry, producing reliable evidence at the molecular level. Its nearly nondestructive nature also preserves the sample for further inquiries. This feature article demonstrates the applicability of ambient mass spectrometry in forensic chemistry and explains the challenges that need to be overcome for this technique to make the ultimate step from the academic world into forensic institutes worldwide.

Paper spray and extraction spray mass spectrometry for the direct and simultaneous quantification of eight drugs of abuse in whole blood.

Determination of eight drugs of abuse in blood has been performed using paper spray or extraction spray mass spectrometry in under 2 min with minimal sample preparation. A method has been optimized for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), morphine, cocaine, and Δ9-tetrahydrocannabinol (THC) from a single blood spot. Sample to sample variations of 1-5% relative standard deviation were achieved using stable isotope-labeled internal standards and tandem mass spectrometry.

Bcrp1;Mdr1a/b;Mrp2 combination knockout mice: altered disposition of the dietary carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and its genotoxic metabolites.

The multidrug transporters breast cancer resistance protein (BCRP), multidrug-resistance protein 1 (MDR1), and multidrug-resistance-associated protein (MRP) 2 and 3 eliminate toxic compounds from tissues and the body and affect the pharmacokinetics of many drugs and other potentially toxic compounds. The food-derived carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is transported by BCRP, MDR1, and MRP2. To investigate the overlapping functions of Bcrp1, Mdr1a/b, and Mrp2 in vivo, we generated Bcrp1;Mdr1a/b;Mrp2(-/-) mice, which are viable and fertile.

Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment.

Purpose: Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported.

P-glycoprotein (ABCB1) transports the primary active tamoxifen metabolites endoxifen and 4-hydroxytamoxifen and restricts their brain penetration.

P-glycoprotein (P-gp, ABCB1) is a highly efficient drug efflux pump expressed in brain, liver, and small intestine, but also in tumor cells, that affects pharmacokinetics and confers therapy resistance for many anticancer drugs. The aim of this study was to investigate the impact of P-gp on tamoxifen and its primary active metabolites, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen. We used in vitro transport assays and Abcb1a/1b(-/-) mice to investigate the impact of P-gp on the oral availability and brain penetration of tamoxifen and its metabolites.