Automated DBS Extraction Prior to Hilic/RP LC–MS/MS Target Screening of Drugs

This article describes a rapid LC–MS/MS target screening method based on an automated extraction of 5 μL dried blood spots (DBS), two 5 min chromatographic runs on orthogonal phase columns (RP and Hilic) and a data dependent acquisition (DDA) of product ions spectra for the reliable identification of the detected compounds. The extraction step was performed in 2 min by using the LC autosampler itself in 96-well plates. This procedure was evaluated using 22 model compounds frequently encountered in forensic investigations, i.e., cocaine, benzodiazepines, amphetamines, opioids, antidepressants and antipsychotics. These investigations showed that even if the extraction step was reduced to a minimum, the extraction recoveries were satisfactory (median value of 40 %) and allowed for the detection of the model compounds in their therapeutic ranges, with the exception of morphine. Moreover, the use of two different chromatographic columns broadened the number of screening targets to those that behaved poorly under RP conditions, such as amphetamines or glucuronides, while keeping chromatographic gradients very short. This procedure was applied to 34 authentic post-mortem cases. It allowed the detection of 89 % of the compounds that were quantified in the routine procedures and the formal identification of 77 % of the compounds using their product ions spectra. These results were considered more than satisfactory compared to routine screening alone (GC–MS and LC-DAD, 55 % compound identification). The method described in this article is therefore a powerful approach for a fast, reliable and efficient target screening of drugs in forensic and clinical investigations.     

A novel method for quantification of sulfolane (a metabolite of busulfan) in plasma by gas chromatography–tandem mass spectrometry

The role of busulfan (Bu) metabolites in the adverse events seen during hematopoietic stem cell transplantation and in drug interactions is not explored. Lack of availability of established analytical methods limits our understanding in this area. The present work describes a novel gas chromatography-tandem mass spectrometric assay for the analysis of sulfolane (Su) in plasma of patients receiving high-dose Bu. Su and Bu were extracted from a single 100 μL plasma sample by liquid-liquid extraction. Bu was separately derivatized with 2,3,5,6-tetrafluorothiophenolfluorinated agent. Mass spectrometric detection of the analytes was performed in the selected reaction monitoring mode on a triple quadrupole instrument after electronic impact ionization. Bu and Su were analyzed with separate chromatographic programs, lasting 5?min each. The assay for Su was found to be linear in the concentration range of 20-400?ng/mL. The method has satisfactory sensitivity (lower limit of quantification, 20?ng/mL) and precision (relative standard deviation less than 15?%) for all the concentrations tested with a good trueness (100?±?5?%). This method was applied to measure Su from pediatric patients with samples collected 4?h after dose 1 (n?=?46), before dose 7 (n?=?56), and after dose 9 (n?=?54) infusions of Bu. Su (mean?±?SD) was detectable in plasma of patients 4?h after dose 1, and higher levels were observed after dose 9 (249.9?±?123.4?ng/mL). This method may be used in clinical studies investigating the role of Su on adverse events and drug interactions associated with Bu therapy.     

Ferromagnetic resonance in monocrystalline spin valves CoFeB/Ta/CoFeB and CoFeB films with perpendicular magnetic anisotropy

Orientation dependences of ferromagnetic resonance in a MgO/CoFeB/MgO/Ta film with one ferromagnetic layer (monolayer) and in a MgO/CoFeB/Ta/CoFeB/MgO/Ta spin valve containing two single-crystal ferromagnetic CoFeB layers divided by a nonmagnetic Ta layer (bilayer) were investigated. Analysis of the orientation dependences of the structures with perpendicular magnetic anisotropy allowed calculating constants of magnetic anisotropy and damping factors. Physical reasons underlying the differences between these parameters in one- and two-layered structures are discussed.     

Narrow band quantitative and multivariate electroencephalogram analysis of peri-adolescent period

ABSTRACT: BACKGROUND: The peri-adolescent period is a crucial developmental moment of transition from childhood to emergent adulthood. The present report analyses the differences in Power Spectrum (PS) of the Electroencephalogram (EEG) between late childhood (24 children between 8 and 13 years old) and young adulthood (24 young adults between 18 and 23 years old). RESULTS: The narrow band analysis of the Electroencephalogram was computed in the frequency range of 0--20 Hz. The analysis of mean and variance suggested that six frequency ranges presented a different rate of maturation at these ages, namely: low delta, delta-theta, low alpha, high alpha, low beta and high beta. For most of these bands the maturation seems to occur later in anterior sites than posterior sites. Correlational analysis showed a lower pattern of correlation between different frequencies in children than in young adults, suggesting a certain asynchrony in the maturation of different rhythms. The topographical analysis revealed similar topographies of the different rhythms in children and young adults. Principal Component Analysis (PCA) demonstrated the same internal structure for the Electroencephalogram of both age groups. Principal Component Analysis allowed to separate four subcomponents in the alpha range. All these subcomponents peaked at a lower frequency in children than in young adults. CONCLUSIONS: The present approaches complement and solve some of the incertitudes when the classical brain broad rhythm analysis is applied. Children have a higher absolute power than young adults for frequency ranges between 0-20 Hz, the correlation of Power Spectrum (PS) with age and the variance age comparison showed that there are six ranges of frequencies that can distinguish the level of EEG maturation in children and adults. The establishment of maturational order of different frequencies and its possible maturational interdependence would require a complete series including all the different ages.     

Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

Competition between domain walls and the reverse magnetization in the magnetic relaxation of a Pt/Co/Ir/Co/Pt spin switcher

A multilayer Pt/Co/Ir/Co/Pt/GaAs heterostructures demonstrates a long term (to several hours) magnetic relaxation between two stable states of the magnetization of the system. The magnetization reversal of the heterostructure layers occurs both due to the formation of nuclei of the reverse magnetization domains and as a result of their further growth by means of motion of domain walls. The competition between two these processes provides a nonexponential character of the magnetic relaxation. At 300 K, the contributions of these processes to the relaxation are commensurable, while, at temperatures lower than 200 K, the contribution of the nucleation is suppressed and the magnetic relaxation occurs as a result of motion of the domain walls.