New neutrino–nucleus interaction cross-section measurements are required to improve nuclear models sufficiently for future long baseline neutrino experiments to meet their sensitivity goals. A time ...projection chamber (TPC) filled with a high-pressure gas is a promising detector to characterise the neutrino sources used for such experiments. A gas-filled TPC is ideal for measuring low-energy particles, which travel further in gas than in solid or liquid detectors and using high-pressure increases the target density, resulting in more neutrino interactions. We examine the suitability of multiwire proportional chambers (MWPCs) from the ALICE TPC for use as the readout chambers of a high-pressure gas TPC. These chambers were previously operated at atmospheric pressure. We report the successful operation of an ALICE TPC outer readout chamber (OROC) at pressures up to 4.2 bar absolute (barA) with
Ar-CH
4
mixtures with a
CH
4
content between 2.8 and 5.0%, and so far up to 4 bar absolute with
Ar-CO
2
(90-10). The charge gain of the OROC was measured with signals induced by an
55
Fe
source. The largest gain achieved at 4.2 bar was
(
29
±
1
)
·
10
3
in
Ar-CH
4
with 4.0%
CH
4
with an anode voltage of
2975
V
. In
Ar-CO
2
with 10%
CO
2
at 4 barA, a gain of
(
4.2
±
0.1
)
·
10
3
was observed with anode voltage
2975
V
. We extrapolate that at 10 barA, an interesting pressure for future neutrino experiments, a gain of 5000 in
Ar-CO
2
with 10%
CO
2
(10,000 in
Ar-CH
4
with
∼
4
%
CH
4
) may be achieved with anode voltage of
4.6
kV
(
∼
3.6
kV
).
•Nine anabolic steroids are separated within 6.4 min and are detectable at 50 fg.•VAMS dried blood exhibits good stability and better recovery over spotting card.•Quantification of testosterone ...between serum and VAMS dried blood is in agreement.•Doping with micro-dose testosterone can be caught by using 20 μL of dried blood.
Anabolic androgenic steroids (AAS) have been the most commonly abused substances taken by not only professional sportsmen but also recreational bodybuilders. The detection of micro-dose testosterone (T) misuse is particularly challenging as it possesses pseudo-endogenous origin and is sometimes impossible to be identified in urine samples. Dried blood (DB) obtained by finger pricking has been proven to be an alternative matrix for better correlating to physiological responses. Moreover, the introduction of the volumetric absorptive microsampling (VAMS) technology allows overcoming some major limitations of spotting blood onto a filter paper card. In this work, a fast and sensitive GC-MS/MS method was developed and validated for the quantification of AAS in DB collected by means of VAMS. T and the eight top abused synthetic AAS, namely nandrolone, boldenone, mesterolone, drostanolone, metenolone, metandienone, oxandrolone, and dehydrochloromethyl T were selected as the target analytes. The method based on VAMS exhibited good precision, accuracy as well as stability, and superior extraction recoveries over the punched DB spots reported in the literature. The chromatographic separation was achieved within 6.4 min and the detection limit is as little as 50 fg (i.e. able to detect 0.10 ng mL−1 in 20 μL of DB). Confirmed by forty real blood samples, the Deming regression and Bland-Altman analysis revealed that the VAMS DB could be employed for quantifying blood T level in agreement with using the serum specimen. The feasibility of the method was then successfully proven by the analysis of samples collected from a three-arm T administration trial. Our results highlighted that DB total T was a sensitive indicator for identifying transdermal micro-dosing of T. In the groups of receiving T gel administration, T concentrations could rise up to ten times higher than the baseline at 9 h after the application. As a future step, this approach is being expanded to a large cohort screening of bodybuilders at gym and ultimately may allow universal applications on monitoring sports drug misuse.
γ-Hydroxybutyric acid (GHB) is a popular drug increasingly associated with cases of drug-facilitated sexual assault (DFSA). Currently, expanding procedures of analysis and having forensic evidence of ...GHB intake in a long term are mandatory. Up to now, most studies have been performed using GC/MS and LC-MS as analytical platforms, which involve significant manipulation of the sample and, often, indirect measurements. In this work, procedures used in NMR-based metabolomics were applied to a GHB clinical trial on urine and serum. Detection, identification, and quantification of the drug by NMR methods were surveyed, as well as the use of NMR-based metabolomics for the search of potential surrogate biomarkers of GHB consumption. Results demonstrated the suitability of NMR spectroscopy, as a robust nondestructive technique, to fast and directly monitor (detect, identify, and quantify) exogenous GHB in almost intact body fluids and its high potential in the search for metabolites associated with GHB intake.
The combination of field asymmetric waveform ion mobility spectrometry with liquid chromatography–mass spectrometry (LC-FAIMS-MS) has been developed for the analysis of glucuronide and sulfate ...metabolites of seven anabolic-androgenic steroids in urine. Separation by FAIMS-MS was investigated in positive ion mode for selected cationic adducts (H+, NH4 +, Na+, K+, and Cs+). LC-FAIMS-MS analysis of the doubly sodiated adducts (M + 2Na – H+) of isobaric and coeluting steroid metabolites allowed their rapid (8 min) qualitative and quantitative determination in spiked urine using hydrophilic interaction liquid chromatography prior to FAIMS-MS separation, with discrimination >95% achieved between the steroids investigated. A quantitative evaluation of the LC-FAIMS-MS method was performed giving limits of detection in the range 1–6 ng mL–1, limits of quantification in the range 3–20 ng mL–1, with reproducibility (%RSD < 10%; n = 6) and linearity (R 2 > 0.99). The LC-FAIMS-MS method demonstrates increases in signal-to-noise ratios for the doubly sodiated steroid metabolites in unspiked urine (>250%) by the reduction of isobaric interferences from the matrix. An alternative or additional tool for identification of the steroid metabolites is based on the observations of different patterns of sodium acetate clusters that are characteristic for each metabolite.
The accuracy and precision of gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) measurements are highly dependent on analyte purity. Reliable analysis of urinary steroids for ...doping control therefore requires extensive and time-consuming sample preparation (i.e. liquid chromatography fraction collection) prior to GC-C-IRMS analysis. The use of two-dimensional GC (GC-GC) with heart-cutting (Deans Switch) as a possible approach to reduce the sample purification required for IRMS analysis is described herein. The system uses a low thermal mass oven (LTM) incorporated into an existing GC-C-IRMS system. GC-GC allowed the use of a cyanopropyl/phenyl column in the first dimension to optimize the separation of underivatized steroids, while a phenyl-methylpolysiloxane column in the second dimension focuses the selectively cut analytes into narrower peaks for more sensitive and reliable MS analysis. In addition, to confirm analyte identity, eluent from the second GC was split, with 20 % entering a scanning MS, and 80 % flowing to the IRMS. As a proof concept, the developed method was then used to analyze a single spot urine (5 ml) from an individual receiving T therapy (2 × 50 mg sachets of Testogel(®)). The T delta value (-27.8 ‰, T = 38 ng/ml) was clearly distinct from 11-ketoetiocholanolone (-22.5 ‰) (used as an endogenous reference compound (ERC)), indicating T as being of exogenous origin. The simultaneous analysis by the scanning MS yielded a full scan mass spectrum of the same chromatographic peak, thus confirming the peak to be T.
Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain ...changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using (11)Ccarfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two (11)Ccarfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in (11)Ccarfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in (11)Ccarfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions.
Over the last 10-15 years, γ-hydroxybutyrate (GHB) and γ-butyrolactone have become increasingly popular "club drugs", but they have also gained attention as potential agents of drug-facilitated ...sexual assault (DFSA). Several studies have attempted to characterize GHB's pharmacokinetic properties in humans, and the aim of this paper is to build on this research with an emphasis on DFSA cases. A 25 mg/kg dose of GHB was given to 12 GHB-naïve volunteers (6 men and 6 women). Urine and blood samples (serum and whole blood) were collected and analyzed by gas chromatography-mass spectrometry following liquid-liquid extraction. The urinary Tmax was 1 h in 11 volunteers with a mean Cmax of 67.6 mg/L (32.6-161.3 mg/L). Urinary concentrations rapidly decreased to < 10 mg/L (interpretive limit) for 11 volunteers after just 4 h. Data derived from whole blood (mean Cmax = 48.0 mg/L, Tmax = 24.6 min) closely matched that from serum (mean Cmax = 59.4 mg/L, Tmax = 23.3 min), suggesting GHB is distributed into erythrocytes. All 12 volunteers had GHB concentrations of less than 5 mg/L in both whole blood and serum after 3 h. Results verify the rapid elimination of GHB and the limited retrospective power of a concentration-based approach to prove GHB administration in blood and urine and confirm that, in DFSA cases, samples should be collected as soon as possible.
PDF
