Quadrupole Mass Spectrometer Research Articles

Simultaneous quantification and confirmation of oxycodone and its metabolites in equine urine using ultra-high performance liquid chromatography-tandem mass spectrometry

Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics of oxycodone and its metabolites in horses, as well as to detect the illegal use of oxycodone in racehorses, a method for quantification and confirmation of oxycodone and its metabolites is needed. In this study, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that can simultaneously quantify and confirm oxycodone and eight metabolites in equine urine. Samples were subjected to enzymatic hydrolysis and then liquid–liquid extraction using ethyl acetate. The analyte separation was achieved on a Hypersil Gold C18 sub-2 µm column and analytes were detected on a triple quadrupole mass spectrometer. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 25–50 pg/mL and 100 pg/mL, respectively. Excellent linearity of the calibration curves was observed over a range of 100–10000 pg/mL for all nine analytes. Retention time, signal-to-noise ratio, and product ion ratios were utilized as confirmation criteria, with the limits of confirmation (LOC) ranging from 100 to 250 pg/mL. The data from a pilot pharmacokinetic (PK) study suggested that oxycodone metabolites have longer detection periods in equine urine compared to oxycodone itself; thus, the detection of metabolites in equine urine extends the ability to detect oxycodone exposure in racehorses.

Assessment of the application of selected metal-organic frameworks as advanced sorbents in passive extraction used in the monitoring of contaminants of emerging concern in surface waters

Water pollution has become a critical global concern requiring effective monitoring techniques and robust protection strategies. Contaminants of emerging concern (CECs) are increasingly detected in various water sources, with their harmful effects on humans and ecosystems continually evolving. Based on literature reports highlighting the promising sorption properties of metal-organic frameworks (MOFs), the aim of this study was to evaluate the suitability of NH2-MIL-125 (Ti) and UiO-66 (Ce) as sorbents in passive sampling devices (MOFs-PSDs) for the collection and extraction of a wide group of CECs. Solvothermal methods were used to synthesize MOFs, and the characterization of the obtained materials was performed using field-emission scanning electron microscopy (FE-SEM), powder X-ray diffractometry (pXRD) and Fourier-transform infrared (FTIR) spectroscopy. The research demonstrated the sorption capabilities of the tested MOFs, the ease and rapidity of their chemical regeneration and the possibility of reuse as sorbents. Using chemometric analysis, the structural properties of CECs determining the sorption efficiency on the surface of NH2-MIL-125 (Ti) were identified. The MOFs-PSDs were lab-calibrated to examine the kinetics of analytes sorption and determine the sampling rates (Rs). MOFs-PSDs and CNTs-PSDs (PSDs containing carbon nanotubes as a sorbent) were then placed in the Elbląg River and the Vistula Lagoon to sampling and extraction of the target compounds from the water. CNTs-PSDs were selected, based on our previous research, for the comparison of the effectiveness of the MOFs-PSDs in environmental monitoring. MOFs-PSDs were successfully used in monitoring of CECs in water. The time-weighted average concentrations (CTWA) of 2-hydroxycarbamazepine, carbamazepine-10,11-epoxide, p-nitrophenol, 3,5-dichlorophenol and caffeine were determined in the Elbląg River and CTWA of metoprolol, diclofenac, 2-hydroxycarbamazepine, carbamazepine-10,11-epoxide, p-nitrophenol, 3,5-dichlorophenol and caffeine were determine in the Vistula Lagoon using MOFs-PSDs and a high-performance liquid chromatography coupled with triple quadrupole mass spectrometer.

The One Hour Human Proteome

We describe deep analysis of the human proteome in less than 1 h. We achieve this expedited proteome characterization by leveraging state-of-the-art sample preparation, chromatographic separations, and data analysis tools, and by using the new Orbitrap Astral mass spectrometer equipped with a quadrupole mass filter, a high-field Orbitrap mass analyzer, and an asymmetric track lossless (Astral) mass analyzer. The system offers high tandem mass spectrometry acquisition speed of 200 Hz and detects hundreds of peptide sequences per second within data-independent acquisition or data-dependent acquisition modes of operation. The fast-switching capabilities of the new quadrupole complement the sensitivity and fast ion scanning of the Astral analyzer to enable narrow-bin data-independent analysis methods. Over a 30-min active chromatographic method consuming a total analysis time of 56 min, the Q-Orbitrap-Astral hybrid MS collects an average of 4319 MS1 scans and 438,062 tandem mass spectrometry scans per run, producing 235,916 peptide sequences (1% false discovery rate). On average, each 30-min analysis achieved detection of 10,411 protein groups (1% false discovery rate). We conclude, with these results and alongside other recent reports, that the 1-h human proteome is within reach.

Comparative Assessment of Lignan Profiling and Biological Activities of Schisandra henryi Leaf and In Vitro PlantForm Bioreactor-Grown Culture Extracts.

This research's scope encompassed biotechnological, phytochemical, and biological studies of Schisandra henryi, including investigations into its in vitro microshoot culture grown in PlantForm bioreactors (temporary immersion systems, TISs), as well as extracts from leaves of the parent plant, focusing on anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The phytochemical analysis included the isolation and quantification of 17 compounds from dibenzocyclooctadiene, aryltetralin lignans, and neolignans using centrifugal partition chromatography (CPC), HPLC-DAD, and UHPLC-MS/MS tandem mass spectrometry with triple quadrupole mass filter methods. Higher contents of compounds were found in microshoots extracts (max. 543.99 mg/100 g DW). The major compound was schisantherin B both in the extracts from microshoots and the leaves (390.16 and 361.24 mg/100 g DW, respectively). The results of the anti-inflammatory activity in terms of the inhibition of COX-1, COX-2, sPLA2, and LOX-15 enzymes indicated that PlantForm microshoot extracts showed strong activity against COX-1 and COX-2 (for 177 mg/mL the inhibition percentage was 76% and 66%, respectively). The antioxidant potential assessed using FRAP, CUPRAC, and DPPH assays showed that extracts from microshoot cultures had 5.6, 3.8, and 3.3 times higher power compared to extracts from the leaves of the parent plant, respectively. The total polyphenol content (TPC) was 4.1 times higher in extracts from the in vitro culture compared to the leaves. The antiproliferative activity against T-cell lymphoblast line Jurkat, breast adenocarcinoma cultures (MCF-7), colon adenocarcinoma (HT-29), and cervical adenocarcinoma (HeLa), showed that both extracts have considerable effects on the tested cell lines. The antimicrobial activity tested against strains of Gram-positive and Gram-negative bacteria and fungi showed the highest activity towards H. pylori (MIC and MBC 0.625 mg/mL).

MEMS quadrupole mass spectrometer

This paper presents the development results of MEMS-based miniature Quadrupole Mass Spectrometer (mQMS). The core components required for the analysis – the ion source, mass analyzer, and ion detector – are fabricated in MEMS technology using monocrystalline silicone and borosilicate glass. These components are housed within a 3D-printed package, ensuring mechanical stability and proper alignment of elements. The utilized MEMS Quadrupole mass analyzer, measuring 70 mm in length with internal radius of 500 µm, provides an analysis resolution of 50 and a mass range between 1 and 200 u when operating at 6 MHz. Our work demonstrates that devices miniaturized using MEMS techniques, along with novel 3D printing fabrication methods, present an emerging coupling, enabling the opportunity to develop portable yet powerful instrumentation for a range of applications. This opens new possibilities for on-site, real-time analysis across various fields.

Discovery of a series of portimine-A fatty acid esters in mussels

Vulcanodinium rugosum is a benthic dinoflagellate known for producing pinnatoxins, pteriatoxins, portimines and kabirimine. In this study, we aimed to identify unknown analogs of these emerging toxins in mussels collected in the Ingril lagoon, France. First, untargeted data acquisitions were conducted by means of liquid chromatography coupled to hybrid quadrupole-orbitrap mass spectrometry. Data processing involved a molecular networking approach, and a workflow dedicated to the identification of biotransformed metabolites. Additionally, targeted analyses by liquid chromatography coupled to triple quadrupole mass spectrometry were also implemented to further investigate and confirm the identification of new compounds. For the first time, a series of 13-O-acyl esters of portimine-A (n = 13) were identified, with fatty acid chains ranging between C12:0 and C22:6. The profile was dominated by the palmitic acid conjugation. This discovery was supported by fractionation experiments combined with the implementation of a hydrolysis reaction, providing further evidence of the metabolite identities. Furthermore, several analogs were semi-synthesized, definitively confirming the discovery of these metabolization products. A new analog of pinnatoxin, with a molecular formula of C42H65NO9, was also identified across the year 2018, with the highest concentration observed in August (4.5 μg/kg). The MS/MS data collected for this compound exhibited strong structural similarities with PnTX-A and PnTX-G, likely indicating a substituent C2H5O2 in the side chain at C33. The discovery of these new analogs will contribute to deeper knowledge of the chemodiversity of toxins produced by V. rugosum or resulting from shellfish metabolism, thereby improving our ability to characterize the risks associated with these emerging toxins.

Understanding associations between antimicrobial agents usage and antimicrobial resistance genes prevalence at the community level using wastewater-based epidemiology: A Spanish pilot study

Understanding the development and spread of antimicrobial resistance (AMR) is important for combating this global threat for public health. Wastewater-based epidemiology (WBE) is a complementary approach to current surveillance programs that minimizes some of the existing limitations. The aim of the present study is to explore WBE for monitoring antibiotics and antibiotic resistance genes (ARGs) in wastewater samples collected during 2021/2022 from the city of Castellon (Spain). Eighteen commonly prescribed antibiotics have been selected and measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), with triple quadrupole mass analysers. Moreover, qPCR for specific ARGs has been performed to obtain information of these genes in co-presence with antibiotics. All selected ARGs, along with a total of 11 antibiotics, were identified. The highest population-normalized daily loads were observed for the macrolide azithromycin, followed by the quinolones ciprofloxacin and levofloxacin. Subsequently, daily consumption estimates based on wastewater data were compared with prescription data of antibiotics. Statistical analyses were conducted to explore if there is correlation between antibiotics and ARGs. While no correlations were found between antibiotics and their corresponding ARGs, certain correlations (p < 0.05) were identified among non-corresponding ARGs. In addition, a strong positive correlation was found between the sum of all antibiotics and the intl1 gene. Moreover, population-normalized ARG loads significantly correlate with the 16S rRNA-normalized ARG loads, serving as an indicator for population size. Results provide a baseline for future work and a proof-of-concept emphasising the need for future work and long-term surveillance, and highlight the need of similar programs at a regional and global levels worldwide.

A fully validated LC‑MS/MS method for quantifyingbevacizumab in plasma samples from patients with NSCLC and its implications in therapeutic drug monitoring.

Given the increasing use of bevacizumab in combinatorial drug therapy for a multitude of different cancer types, there is a need for therapeutic drug monitoring to analyze the possible correlation between drug trough concentration, and therapeutic effect and adverse reactions. An ultra-performance liquid chromatography tandem-mass spectrometry method was then developed and validated to determine bevacizumab levels in human plasma samples. Chromatographic separation was achieved on a Shimadzu InertSustainBio C18 HP column, whereas subsequent mass spectrometric analysis was performed using a Shimadzu 8050CL triple quadrupole mass spectrometer equipped with an electro-spray ionization source in the positive ion mode. In total, three multiple reaction monitoring transitions of each of the surrogate peptides were chosen with 'FTFSLDTSK' applied as the quantification peptide whereas 'VLIYFTSSLHSGVPSR' and 'STAYLQMNSLR' were designated as the verification peptides using the Skyline software. This analytical method was then fully validated, with specificity, linearity, lower limit of quantitation, accuracy, precision, stability, matrix effect and recovery calculated. The linearity of this method was developed to be within the concentration range 5-400 µg/ml for bevacizumab in human plasma. Subsequently, eight patients with non-small cell lung cancer (NSCLC) were recruited and injected with bevacizumab over three periods of treatment to analyze their steady-state trough concentration and differences. To conclude, the results of the present study suggest that bevacizumab can be monitored in a therapeutic setting in patients with NSCLC.

Development and validation of an LC-MSMS method to quantify creatinine from dried blood spots

IntroductionScreening for chronic kidney disease relies on accurate and precise creatinine measurements. Traditionally, creatinine is measured in serum or plasma using high-throughput chemistry analyzers. However, dried blood spots (DBS) can also be utilized to improve testing access. MethodsSamples were obtained from a 6 mm DBS punch, which was reconstituted in water before undergoing an acetonitrile crash. The resulting supernatant was diluted using an 80:20 acetonitrile: water before injection. Creatinine was identified using an isocratic gradient, and detected using an API 4000 triple quadrupole mass analyzer. Quantification relied on matrix-matched calibrators, with values harmonized to the Roche Cobas enzymatic assay. Validation studies assessing method performance included precision, linearity, accuracy, method comparison, stability, interference, and matrix effects. ResultsThe LC-MSMS assay was linear from 0.3 to 20 mg/dL (y = 1.02x-0.11; R2 = 0.996). Precision ranged from 5.2 to 8.1 % using matrix-matched controls (n = 4) that spanned the analytical measurement range. LC-MSMS results corresponded to the enzymatic assay (Roche) with a fitted line equation of y = 0.956x–0.07 (R2 = 0.995; n = 173). The Siemens and Roche enzymatic assays demonstrated higher accuracy in correlating to the DBS creatinine concentration (n = 40 paired venous/DBS collections) compared to the Beckman Jaffe assay (-2.5 % and −0.8 % versus −6.3 % and −4.1 %, respectively) or the iSTAT (-28.4 % and −27.1 %, respectively). Accuracy was unaffected by hematocrit, blood spot volume, excess IgG or IgA, or hypertriglyceridemia. No matrix effects were observed, and both extraction and processing efficiency were robust.Ambient stability extended to at least 10 days, and exposure to extreme temperature did not affect the creatinine results. ConclusionWe successfully developed an accurate and precise LC-MSMS method for quantifying creatinine in DBS.

Evaluating Atmospheric and Surface Drivers for O2 Variations at Gale Crater as Observed by MSL SAM

We explore and evaluate various processes that could drive the variations in the volume mixing ratio (VMR) of atmospheric O2 observed by the quadrupole mass spectrometer (QMS) of the Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) Curiosity rover. First reported by Trainer et al. (), these ∼20% variations in the O2 VMR on a seasonal timescale over Mars Years 31–34, in excess of circulation and transport effects driven by the seasonal condensation and sublimation of CO2 at the poles, are significantly shorter than the modeled O2 photochemical lifetime. While there remains significant uncertainty about the various processes we investigated (atmospheric photochemistry, surface oxychlorines and H2O2, dissolution from brines, and airborne dust), the most plausible driver is surface oxychlorines, exchanging O2 with the atmosphere through decomposition by solar ultraviolet and regeneration via O3. A decrease in O3 from increased atmospheric H2O would reduce the removal rate of O2 from the atmosphere to form oxychlorines at the surface. This is consistent with the tentative observation that increases in O2 are associated with increases in water vapor. A lack of correlation with the local surface geology along Curiosity’s traverse within Gale crater, the nonuniqueness of the relevant processes to Gale crater, and the short mixing timescales of the atmosphere all suggest that the O2 variations are a regional, or even global, phenomenon. Nonetheless, further laboratory experiments and modeling are required to accurately scale the laboratory-measured rates to Martian conditions and to fully elucidate the driving mechanisms.

In Situ Chlorine Generation and Rare Earth Chlorination by Molten Salt Electrolysis

Chloride volatility processes for purifying actinide and rare earth elements have historically required the use of Cl2 tanks. To minimize the hazards associated with these processes, an apparatus was designed to produce Cl2 via molten salt electrolysis. Within this apparatus, one can generate Cl2, chlorinate metals, and consume excess Cl2. Here, electrode materials were tested for their ability to generate Cl2, the composition of the gaseous electrolysis product was evaluated using a quadrupole mass spectrometer, and a Ce foil sample was successfully chlorinated using the electrochemically generated Cl2.

A quantitative LC-MS/MS analysis of Xylazine, p-Fluorofentanyl, Fentanyl and Fentanyl-Related compounds in postmortem blood

The purpose of this study was to develop and validate a method to quantitate the veterinary sedative xylazine as well as 4-anilino-N-phenethylpiperidine (4-ANPP), acetyl fentanyl, fentanyl, norfentanyl, and p-fluorofentanyl in blood utilizing liquid chromatography tandem mass spectrometry. This method also qualitatively monitors for the presence of o-fluorofentanyl and m-fluorofentanyl isomers. UCT Clean Screen® DAU extraction columns were utilized to isolate the analytes in postmortem blood samples. The extracts were eluted, evaporated, reconstituted, and then analyzed using a Waters Acquity™ UPLC coupled a triple quadrupole mass spectrometer. The lower limit of quantitation was determined to be 0.1 ng/mL for all analytes, except for xylazine (0.2 ng/mL). The upper limit of quantitation for all analytes was 100 ng/mL. No interferences from matrix, internal standard, or common drug analytes were observed. Bias (-13.1–4.6 %) and precision (-13.14–10.3 %) fell within the acceptable ± 20 % criteria range. Dilution integrity at x2, x10, and x100 was evaluated and all results were within ± 20 % of the target concentration. Processed extract stability was evaluated after 72 h and all results were within ± 20 % of the analyte initial concentration. Matrix effects were the most prominent with xylazine, but deemed acceptable as the deuterated internal standard also observed comparable enhancement. Analysis of 89 postmortem blood samples by this method resulted in positive results for fentanyl (0.27–66 ng/mL, n = 82), xylazine (0.24–958 ng/mL, n = 21), 4-ANPP (0.10–38 ng/mL, n = 72), acetyl fentanyl (0.18–1.5 ng/mL, n = 3), p-fluorofentanyl (0.11–33 ng/mL, n = 30), and norfentanyl (0.10–98 ng/mL, n = 73).

Pharmacokinetic and tissue distribution analysis of bioactive compounds from Fuke Qianjin capsules in rats by a validated UPLC[sbnd]MS/MS method

Fuke Qianjin capsules (FKQJ) exhibit obvious advantages and characteristics in the treatment of pelvic inflammatory disease. At present, information regarding the in vivo process of FKQJ is lacking, which has become a bottleneck in further determining the therapeutic effect of this traditional Chinese medicine. In the present study, a sensitive, simple and reliable method was developed and validated for the simultaneous quantification of 12 main components (4 flavonoids, 4 alkaloids, 2 phthalides and 2 diterpene lactones) in plasma and seven tissues of rats to study the pharmacokinetic and distribution characteristics of these components in vivo by using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the first time. Plasma and tissue were prepared by protein precipitation with acetonitrile and methanol, followed by its separation on a Waters Acquity UPLC BEH C18 column. The quantification was performed via multiple reaction monitoring (MRM) by a triple quadrupole mass spectrometer under positive electrospray ionization (ESI) mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect and stability. For 12 analytes, the low limit of quantification (LLOQs) reached 0.005–2.44 ng/mL, and all calibration curves showed good linearity (r2 ≥ 0.990) in linear ranges. The intra-day and inter-day precision (relative standard deviation) for all analytes was less than 14.96%, and the accuracies were in the range of 85.29%−114.97%. Extraction recoveries and matrix effects of analytes were acceptable. The pharmacokinetic results showed that the main components could be absorbed quickly, had a short residence time, and were eliminated quickly in vivo. At different time points, the 12 components were widely distributed with uneven characteristics in the body, which tended to be distributed in the liver, kidney and lung and to a lesser extent in the uterus, brain and heart. The pharmacokinetic process and tissue distribution characteristics of FKQJ were expounded in this study, which can provide a scientific theory for in-depth development of FKQJ and guide FKQJ use in the clinic.

Coupling thin layer chromatography with mass spectrometry for detection and identification of sertraline and its metabolite in the urine

The aim of the study was to detect sertraline and its metabolites in urine under standardized thin layer chromatography (TLC) screening conditions and identify the metabolites using the mass spectrometry method. Materials and methods. Urine samples, collected within 30 hours in portions of 20–50 mL, commenced from the seventh hour after the administration of a single therapeutic dose of the drug. The sample preparation process involved dilute acid hydrolysis, followed by the extraction of the native compound and metabolites with chloroform at a pH of 8–9. Thin layer chromatography studies of the extracts were conducted using four unified TLC systems recommended by The International Association of Forensic Toxicologists for general drug screening. Chromatograms were subjected to color reactions with a variety of chromogenic reagents. For the analysis of eluates from chromatograms, a Varian 1200 L mass spectrometer (Netherlands) equipped with a dual quadrupole mass analyzer was employed. Identification was performed through direct sample introduction into the ion chamber, electron-impact ionization (70 eV), and full ion scanning mode. Results. The spot of the native drug on the chromatogram was identified by the Rf, value. Metabolite of sertraline was identified as N-desmethyltrihydroxysertraline by the molecular ion peak in the mass spectrum. Conclusions. The study demonstrated the ability of TLC to detect sertraline and its metabolite, N-desmethyltrihydroxysertraline, in urine after the administration of a single therapeutic dose of the drug. The chromatographic mobility of the native compound and N-desmethyltrihydroxysertraline in the unified TLC screening systems, along with the results of their visualization using chromogenic reagents for toxicological drug screening, was determined. Furthermore, the potential of coupling TLC with mass spectrometry for the separation, detection, and confirmatory identification of sertraline and its metabolic products in urine was established.

Hydrogen Chloride and Sulfur Dioxide Gas Evolutions from the Reaction between Mg Sulfate and NaCl: Implications for the Sample Analysis at the Mars Instrument in Gale Crater, Mars

The Sample Analysis at Mars-Evolved Gas Analyzer (SAM-EGA) on the Curiosity rover detected hydrogen chloride (HCl) and sulfur dioxide (SO2) gas evolutions above 600 °C and 700 °C, respectively, from several drilled rock and soil samples collected in Gale crater, which have been attributed to NaCl and Mg sulfates. Although NaCl and Mg sulfates do not evolve HCl or SO2 within the SAM temperature range (&lt;~870 °C) when analyzed individually, they may evolve these gases at &lt;870 °C and become detectable by SAM-EGA when mixed. This work aims to determine how Mg sulfate and NaCl interact during heating and how that affects evolved HCl and SO2 detection temperatures in SAM-EGA. Solid mixtures of NaCl and kieserite were analyzed using a thermogravimeter/differential scanning calorimeter furnace connected to a quadrupole mass spectrometer, configured to operate under similar conditions as SAM, and using X-ray diffraction of heated powders. NaCl analyzed individually did not evolve HCl; however, NaCl/kieserite mixtures evolved HCl releases with peaks above 600 °C. The results suggested that kieserite influenced HCl production from NaCl via two mechanisms: (1) kieserite depressed the melting point of NaCl, making it more reactive with evolved water; and (2) SO2 from kieserite decomposition reacted with NaCl and water (i.e., Hargreaves reaction). Additionally, NaCl catalyzed the thermal decomposition of kieserite, such that the evolved SO2 was within the SAM-EGA temperature range. The results demonstrated that SAM-EGA can detect chlorides and Mg sulfates when mixed due to interactions during heating. These phases can provide information on past climate and mineral formation conditions.

Therapeutic drug monitoring of clozapine in human serum by high-throughput paper spray mass spectrometry

IntroductionMonitoring the atypical antipsychotic drug clozapine is crucial to ensure patient safety. This article showcases a high-throughput analytical method for measuring clozapine and its primary metabolite norclozapine (N-desmethylclozapine) in serum using paper spray mass spectrometry (PS-MS). ObjectivesThis study aimed to assess the viability of a PS-MS method for the rapid measurement of clozapine and norclozapine in human serum samples as an alternative to liquid chromatography mass spectrometry (LC-MS). MethodsSerum samples were processed by protein precipitation followed by deposition of the supernatant containing labelled internal standards onto paper spray substrates mounted in cartridges. Analytes were then analyzed using a triple quadrupole mass spectrometer equipped with a commercial paper spray ionization source. The results obtained from the patient samples were compared to those from a validated LC-MS assay. ResultsPS-MS calibrations for clozapine and norclozapine were linear (R2 > 0.99) over five days. Between-run precision was below 8 %, and within-run precision did not exceed 10 %. When compared to a validated LC-MS method, the mean bias for 39 patient samples was −9% for clozapine and −1% for norclozapine, with no outliers. Mass spectrometry ion ratio comparisons indicated no interference for patient samples above the lower limit of quantification. There was less than 7 % change in the measured concentrations of both analytes over five days for samples dried on paper substrates. Notably, virtually no maintenance of the MS source was required during this study. ConclusionThis study illustrates the potential of PS-MS for serum drug monitoring in the clinical laboratory.

Strategies to detect trace methamphetamine contamination on hard surfaces: Assessing realistic performance of commercially available presumptive tests and a laboratory-based LC-MS/MS method.

Recreational methamphetamine production and heavy use can result in dwelling contamination that is difficult to detect. First responders and public health officials may use commercially available trace methamphetamine detection (presumptive) test kits to understand apparent and hidden dangers in impacted dwellings. Here, we assessed the limit of detection (LOD) of several commercially available presumptive test kits using simulated contaminated hard surfaces. Pyrex petri dishes were spiked with aliquots of methanolic methamphetamine solutions to reach desired simulated contamination levels. Commercially available presumptive tests were conducted according to manufacturer instructions and using included sample preparation materials, when available. Additionally, a laboratory-based liquid chromatography-triple quadrupole mass spectrometer (LC-MS/MS) trace methamphetamine quantification method was developed and validated using the EZSTATSG2 tool. For the LC-MS/MS method, samples were collected using 2-ply alcohol prep pads and methamphetamine was extracted using a 1:1 (v:v) methanol: water solution. Most presumptive tests considered were able to detect trace levels of methamphetamine extracted from hard surfaces, with LOD ranging from 0.10-15.00 μg/sample. Comparatively, the laboratory-based LC-MS/MS LOD was 0.05 μg/sample and limit of quantitation was 0.10 μg/sample. The LC-MS/MS method may be useful when the presence of dust or other contaminants interferes with presumptive test interpretation or reliability. Costs of presumptive tests varied from several dollars to tens of dollars, which is included alongside LOD results to aid stakeholders in identifying which test(s) are the best fit for purpose. Therefore, first responders, public health officials, and other stakeholders have several options for assessing trace methamphetamine contamination.

Axial Concentration of Dissolved Deuterium by Dispersion in a LiPb Experimental Loop

The axial concentration of deuterium by dispersion in a circulating liquid lithium-lead (LiPb) loop was analyzed and experimentally verified. In previous fusion blanket studies, the tritium transport rate in flowing LiPb was treated by convection a priori; i.e., the dispersion effect was negligible. In contrast, Taylor dispersion theory shows conflicting results, exhibiting axial transport enhancement via convective flow. In the current paper, the experimental setup consists of a deuterium dissolving tube that substitutes for tritium breeding and a deuterium concentration monitor by LiPb droplets in a vacuum with four nozzles of ϕ = 1.0 mm. The released deuterium mass flux from the droplets was measured using a quadrupole mass spectrometer. An electromagnetic pump circulated 49 L of LiPb at 350°C at a rate between 0.15 and 0.3 L∙min–1 with the corresponding Re number between 600 and 1000, i.e., in the laminar flow range. The dispersion coefficient was analyzed by measuring the temporal distortion of the deuterium concentration profile. The obtained axial dispersion coefficients of dissolved deuterium in LiPb were between 4.6 × 10–2 and 1.2 × 10–1 (m2∙s–1) and approximately seven orders of magnitude greater than those under static conditions. The results agreed with the Taylor dispersion theory, which studied the mass transport enhancement by convection. The applicability of Taylor’s theory to the deuterium flow in liquid LiPb is suggested, whereas the Prandtl number was three orders of magnitude lower and the Schmidt number was one order of magnitude higher than that of the water.

Simultaneous quantification of four hormone therapy drugs by LC-MS/MS: Clinical applications in breast cancer patients

IntroductionAromatase inhibitors such as anastrozole, letrozole, exemestane and selective estrogen down-regulator (SERD) fulvestrant are used mostly to treat breast cancer estrogen receptor positive in post-menopausal women. These drugs are given either through the oral route or by intramuscular injection. They have shown great inter-individual variability with a risk of cardiometabolic disorders. Hence the importance of their therapeutic drug monitoring not only for exposure-efficacy but also exposure-toxicity. We describe here a LC-MS/MS method for the simultaneous quantification of anastrozole, letrozole, exemestane and fulvestrant in human plasma. Material and methodsPlasma samples were prepared by a single-step protein precipitation. The liquid chromatography system was paired with a triple quadrupole mass spectrometer. Quantification were achieved in Multiple Reactions Monitoring mode and the electrospray ionization was in positive mode. ResultsThe method demonstrated consistent analytical performance across various parameters, including linearity, specificity, sensitivity, matrix effect, upper and lower limits of quantification, extraction recovery, precision, accuracy, hemolysis effect, dilution integrity, and stability under different storage conditions, in accordance with established guidelines. The analysis time for each run was 4 min. Calibration curves exhibited linearity within the 1–100 ng/mL range, with correlation coefficients > 0.99 for the four analytes. Plasma concentrations from 42 patients were integrated into the selected calibration. Stability assessments indicated that the four drugs remained stable at − 20 °C for three months, 15 days under refrigeration, up to 7 days at room temperature, and after three freeze-thaw cycles. ConclusionWe have developed and validated this quantitative method for therapeutic drug monitoring of those four hormone therapy drugs:anastrozole, letrozole, fulvestrant and exemestane. This method can be also used for future clinical pharmacokinetics /pharmacodynamics studies.

Lipid Isobar and Isomer Imaging Using Nanospray Desorption Electrospray Ionization Combined with Triple Quadrupole Mass Spectrometry.

Mass spectrometry imaging (MSI) is widely used for examining the spatial distributions of molecules in biological samples. Conventional MSI approaches, in which molecules extracted from the sample are distinguished based on their mass-to-charge ratio, cannot distinguish between isomeric species and some closely spaced isobars. To facilitate isobar separation, MSI is typically performed using high-resolution mass spectrometers. Nevertheless, the complexity of the mixture of biomolecules observed in each pixel of the image presents a challenge, even for modern mass spectrometers with the highest resolving power. Herein, we implement nanospray desorption electrospray ionization (nano-DESI) MSI on a triple quadrupole (QqQ) mass spectrometer for the spatial mapping of isobaric and isomeric species in biological tissues. We use multiple reaction monitoring acquisition mode (MRM) with unit mass resolution to demonstrate the performance of this new platform by imaging lipids in mouse brain and rat kidney tissues. We demonstrate that imaging in MRM mode may be used to distinguish between isobaric phospholipids requiring a mass resolving power of 3,800,000. Additionally, we have been able to image eicosanoid isomers, a largely unexplored class of signaling molecules present in tissues at low concentrations, in rat kidney tissue. This new capability substantially enhances the specificity and selectivity of MSI, enabling spatial localization of species that remain unresolved in conventional MSI experiments.