Microsampling Method Research Articles

Next generation microsampling towards sustainable forensic analysis: Volumetric DBS for cocaine and metabolites

This study introduces for the first time a reliable whole blood microsampling method for forensic analysis of cocaine and its metabolites using quantitative dried blood spot (qDBS) technology and UHPLC-MS analysis. This methodology offers accurate and less invasive sampling and aligns with the current trend towards sustainable and accessible analytical methods. Microsampling is subject-friendly, improves logistics, stability and efficiency, marking a shift towards modern forensic practices with wide-ranging application potential.The qDBS-UHPLC-MS method underwent comprehensive validation, confirming its linearity, sensitivity, precision, extraction efficiency and stability. UHPLC-MS achieved effective chromatographic separation and suitable sensitivity, with detection limits between 1.0 and 2.5 ng/mL, and quantitation limits from 2.5 to 7.5 ng/mL. Analytes showed over 85.1 % extraction yield and less than 7.5 % relative standard deviation in precision. Stability tests indicated superior analyte preservation in qDBS at room temperature versus refrigerated plasma, while minimal matrix effect highlighted the sample clean-up efficiency. Application to real samples yielded consistent quali-quantitative results between qDBS and plasma samples, confirming method suitability for forensic cocaine bioanalysis, thus addressing critical needs in drug testing and pharmaco-toxicological analysis.

Case study observational research: inflammatory cytokines in the bronchial epithelial lining fluid of COVID-19 patients with acute hypoxemic respiratory failure

BackgroundIn this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19).MethodsWe comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation.ResultsCompared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1β were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1β (202), IL-31 (169), MCP-1 (81), MIP-1β (55), and TNF-α (47) were lower.ConclusionsThe ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1β were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.

New material connections in a mother-of-pearl Enconchado from the Viceroyalty of New Spain

Adoration of the Magi (ca. 1695–1700), an enconchado painting attributed to Miguel González, active in Mexico in the late seventeenth century, exemplifies the refinement of the arts produced in Spanish America as a response to the taste for Asian goods during the seventeenth and eighteenth centuries. The painting and its original mother-of-pearl inlaid frame were examined and analyzed using non-invasive and micro-sampling methods, an approach that permitted answering outstanding questions about the stratigraphy, pigments, and the use of shells throughout the painting and frame. The identification of the mother-of-pearl, determined to be from a Pinctada species, was a central focus of this study. In addition to the inlaid shells in the painting and frame, shell fragments were observed mixed with gypsum in the ground preparation of the painting by SEM–EDS. To our knowledge, this is a novel identification of marine shells in the ground of an easel painting. Traces of workmanship in the inlaid shells observed by SEM and optical microscopy are possibly connected to pre-Hispanic methodologies of mother-of-pearl refinement.Graphical

Analytical Validation of a Volumetric Absorptive Microsampling Method for Therapeutic Drug Monitoring of the Oral Targeted Anticancer Agents, Abiraterone, Alectinib, Cabozantinib, Imatinib, Olaparib, and Sunitinib, and Metabolites.

Volumetric Absorptive Microsampling (VAMS) is a useful tool for therapeutic drug monitoring (TDM) of oral targeted anticancer agents. VAMS aims to improve safety and efficacy by enabling at-home blood sample collection by patients. This study aimed to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometry method for the quantitative determination of abiraterone, alectinib, cabozantinib, imatinib, olaparib, sunitinib, and the metabolites, Δ(4)-abiraterone (D4A), alectinib-M4, imatinib-M1, and N -desethyl sunitinib, in dried whole blood samples using VAMS to support TDM. After the collection of 10 μL of whole blood sample using the VAMS device, the analytes were extracted from the tip using methanol with shaking, evaporated, and reconstituted in acetonitrile:0.1 mol/L ammonium hydroxide in water (1:1, vol/vol). The extracts were then analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. Validation experiments based on the ICH M10 guideline were carried out, and stability was evaluated under shipping and storage conditions. VAMS specimens were collected in the outpatient clinic to demonstrate the applicability of the assay. The validated range of the method was considered accurate and precise for all analytes. Accordingly, the validation experiments met the relevant requirements, except for cross-analyte interference. Based on the stability data, shipment can be performed at room temperature within 14 days after sample collection and the VAMS specimen can be stored up to 9 months at -20 and -70°C. Samples from 59 patients were collected at the hospital. The developed method could be used to successfully quantify the concentrations of abiraterone, D4A, alectinib, alectinib-M4, cabozantinib, imatinib, imatinib-M1, olaparib, sunitinib, and N -desethyl sunitinib within the validated range using VAMS. Therefore, the method can be used to estimate the dried whole blood-to-plasma ratios for TDM in the clinic.

Patient-Centric Quantitative Microsampling for Accurate Determination of Urine Albumin to Creatinine Ratio (UACR) in a Clinical Setting.

Developing and implementing new patient-centric strategies for drug trials lowers the barrier to participation for some patients by reducing the need to travel to research sites. In early chronic kidney disease (CKD) trials, albuminuria is the key measure for determining treatment effect prior to pivotal kidney outcome trials. To facilitate albuminuria sample collection outside of a clinical research site, we developed 2 quantitative microsampling methods to determine the urinary albumin to creatinine ratio (UACR). Readout was performed by LC-MS/MS. For the Mitra device the within-batch precision (CV%) was 2.8% to 4.6% and the between-batch precision was 5.3% to 6.1%. Corresponding data for the Capitainer device were 4.0% to 8.6% and 6.7% to 9.0%, respectively. The storage stability at room temperature for 3 weeks was 98% to 103% for both devices. The recovery for the Mitra and Capitainer devices was 104% (SD 7.0%) and 95 (SD 7.4%), respectively. The inter-assay comparison of UACR assessment generated results that were indistinguishable regardless of microsampling technique. The accuracy based on LC-MS/MS vs analysis of neat urine using a clinical chemistry analyzer was assessed in a clinical setting, resulting in 102 ± 8.0% for the Mitra device and 95 ± 10.0% for the Capitainer device. Both UACR microsampling measurements exhibit excellent accuracy and precision compared to a clinical chemistry analyzer using neat urine. We applied our patient-centric sampling strategy to subjects with heart failure in a clinical setting. Precise UACR measurements using quantitative microsampling at home would be beneficial in clinical drug development for kidney therapies.

Dried Raw Camel Milk Spot (“DRCMS”) as a Simple and Efficient Microsampling Method from Hot and Remote Regions for Mesophilic Aerobe Count and Lactofermentation Microbiota Activity Detection

Dried Raw Camel Milk Spot (“DRCMS”) as a Simple and Efficient Microsampling Method from Hot and Remote Regions for Mesophilic Aerobe Count and Lactofermentation Microbiota Activity Detection

Applications of Volumetric Absorptive Microsampling Technique: A Systematic Critical Review.

A novel microsampling device called Volumetric Absorptive microsampling (VAMS), developed in 2014, appears to have resolved the sample inhomogeneity inherent to dried blood spots, with improved precision in the volume of sample collected for measuring drug concentration. A literature search was conducted to identify several analytical and pharmacokinetic studies that have used VAMS in recent years. The key factors for proper experimental design and optimization of the extraction of drugs and metabolites of interest from the device were summarized. This review focuses on VAMS and elaborates on bioanalytical factors, method validation steps, and scope of this technique in clinical practice. The promising microsampling method VAMS is especially suited for conducting pharmacokinetic studies with very small volumes of blood, especially in special patient populations. Clinical validation of every VAMS assay must be conducted prior to the routine practical implementation of this method.

Fingerprick Microsampling Methods Can Replace Venepuncture for Simultaneous Therapeutic Drug Monitoring of Tacrolimus, Mycophenolic Acid, and Prednisolone Concentrations in Adult Kidney Transplant Patients.

Kidney transplant patients undergo repeated and frequent venepunctures during allograft management. Microsampling methods that use a fingerprick draw of capillary blood, such as dried blood spots (DBS) and volumetric absorptive microsamplers (VAMS), have the potential to reduce the burden and volume of blood loss with venepuncture. This study aimed to examine microsampling approaches for the simultaneous measurement of tacrolimus, mycophenolic acid, mycophenolic acid glucuronide (MPAG), and prednisolone drug concentrations compared with standard venepuncture in adult kidney transplant patients. DBS and VAMS were simultaneously collected with venepuncture samples from 40 adult kidney transplant patients immediately before and 2 hours after immunosuppressant dosing. Method comparison was performed using Passing-Bablok regression, and bias was assessed using Bland-Altman analysis. Drug concentrations measured through microsampling and venepuncture were also compared by estimating the median prediction error (MPE) and median absolute percentage prediction error (MAPE). Passing-Bablok regression showed a systematic difference between tacrolimus DBS and venepuncture [slope of 1.06 (1.01-1.13)] and between tacrolimus VAMS and venepuncture [slope of 1.08 (1.03-1.13)]. Tacrolimus values were adjusted for this difference, and the corrected values showed no systematic differences. Moreover, no systematic differences were observed when comparing DBS or VAMS with venepuncture for mycophenolic acid and prednisolone. Tacrolimus (corrected), mycophenolic acid, and prednisolone microsampling values met the MPE and MAPE predefined acceptability limits of <15% when compared with the corresponding venepuncture values. DBS and VAMS, collected in a controlled environment, simultaneously measured multiple immunosuppressants. This study demonstrates that accurate results of multiple immunosuppressant concentrations can be generated through the microsampling approach, with a preference for VAMS over DBS.

3D Surface Reconstruction Method for Microsamples Based on Polarization Modulation Microscopy

A novel microscopic Shape-From-Polarization (SFP) 3D shape reconstruction method is proposed, in which degree of polarization is calculated using Polarized Bidirectional Reflectance Distribution Function (PBRDF) to overcome azimuthal ambiguity for both specular and diffuse polarization microscopic scenes. Based on the calculated degree of polarization, a polarization modulation microscopy oriented variational model is established to estimate surface normal vector and rebuild 3D shape of the sample with “fuzzy guidance” based on atomic force microscopy (AFM). Experiments on different microscopic samples indicate the proposed method can restore the stereoscopic morphology distribution with precision in micrometer.

Applicability of vancomycin, meropenem, and linezolid in capillary microsamples vs. dried blood spots: A pilot study for microsampling in critically ill children.

Therapeutic drug monitoring (TDM) has been shown to be clinically beneficial for critically ill patients. However, this is a burden for neonates or children with small circulating blood volumes. Here, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem, and linezolid. Paired DBS and CMS samples were obtained from an intensive care unit (ICU) to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland-Altman difference plots. The microsampling methods validation showed excellent reliability and compatibility with the analysis of the sample matrix and hematocrit range of the studied population. The DBS and CMS accuracy and precision results were within accepted ranges and samples were stable at room temperature for at least 2 days and 8 h, respectively. Hematocrit had no impact on CMS, but sightly impacted DBS measurements. The CMS and DBS antibiotic concentrations correlated well (r > 0.98). The drug concentration ratio in DBS samples to that in CMS was 1.39 for vancomycin, 1.34 for meropenem, and 0.94 for linezolid. The EPC calculated from the DBS using individual hematocrit ranges presented comparable absolute values for vancomycin (slope: 1.06) and meropenem (slope: 1.04), with a mean of 98% and 99% of the measured CMS concentrations, respectively. This study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.

Volumetric Absorptive Microsampling in Therapeutic Drug Monitoring of Immunosuppressive Drugs-From Sampling and Analytical Issues to Clinical Application.

Miniaturisation and simplification are novel approaches in clinical bioanalysis, especially in therapeutic drug monitoring (TDM). These contemporary trends are related to the sampling, pre-treatment, and analysis of biological fluids. Currently, dried blood spot (DBS), one of the most popular microsampling techniques, is feasible and inexpensive. However, obtaining reliable results with sample homogeneity and volume variability is difficult. Volumetric Absorptive Microsampling (VAMS) has recently enabled the accurate and precise collection of a fixed blood volume. It reduced the hematocrit effect, improved volumetric accuracy, and generated results correlating with the dose and drug exposure from wet blood. This review focuses on VAMS-Mitra™ devices, which have become increasingly important since 2014, mainly for TDM and toxicology studies. First, the current literature has been reviewed based on immunosuppressants and their determination in samples obtained using Mitra™. Second, the critical points, weaknesses, and strengths have been characterized in contrast to classic venipuncture and other microsampling methods. Finally, we indicate the points of attention according to the perspective of Mitra™ as well as its usefulness in clinical practice. VAMS is currently state-of-the-art in microsampling and seems to be a good instrument for improving adherence to immunosuppressive therapy, especially in the pediatric population.

Micro-fractionation shows microbial community changes in soil particles below 20 μm

IntroductionMicro-scale analysis of microbes in soil is essential to the overall understanding of microbial organization, interactions, and ecosystem functioning. Soil fractionation according to its aggregated structure has been used to access microbial habitats. While bacterial communities have been extensively described, little is known about the fungal communities at scales relevant to microbial interactions.MethodsWe applied a gentle soil fractionation method to preserve stable aggregated structures within the range of micro-aggregates and studied fungal and bacterial communities as well as nitrogen cycling potentials in the pristine Rothamsted Park Grass soil (bulk soil) as well as in its particle size fractions (PSFs; &amp;gt;250 μm, 250–63 μm, 63–20 μm, 20–2 μm, &amp;lt;2 μm, and supernatant).ResultsOverall bacterial and fungal community structures changed in PSFs below 20 μm. The relative abundance of Basidiomycota decreased with decreasing particle size over the entire measure range, while Ascomycota showed an increase and Mucoromycota became more prominent in particles below 20 μm. Bacterial diversity was found highest in the &amp;lt; 2 μm fraction, but only a few taxa were washed-off during the procedure and found in supernatant samples. These taxa have been associated with exopolysaccharide production and biofilm formation (e.g., Pseudomonas, Massilia, Mucilaginibacter, Edaphobaculum, Duganella, Janthinobacterium, and Variovorax). The potential for nitrogen reduction was found elevated in bigger aggregates.DiscussionThe observed changes below 20 μm particle are in line with scales where microbes operate and interact, highlighting the potential to focus on little researched sub-fractions of micro-aggregates. The applied method shows potential for use in studies focusing on the role of microbial biofilms in soil and might also be adapted to research various other soil microbial functions. Technical advances in combination with micro-sampling methods in soil promise valuable output in soil studies when particles below 20 μm are included.

Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients.

Cannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to Δ9-tetrahydrocannabinol (THC). While recreational cannabis contains higher THC and lower CBD concentrations, medical cannabis contains THC and CBD in different ratios, along with minor phytocannabinoids, terpenes, flavonoids and other chemicals. A volumetric absorptive microsampling (VAMS) method combined with ultra-high-performance liquid chromatography coupled with mass spectrometry in tandem for quantification of CBD, THC and their respective metabolites: cannabidiol-7-oic acid (7-COOH-CBD); 7-hydroxy-cannabidiol (7-OH-CBD); 6-alpha-hydroxy-cannabidiol (6-α-OH-CBD); and 6-beta-hydroxycannabidiol (6-β-OH-CBD); 11- Hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH). After overnight enzymatic glucuronide hydrolysis at 37°C, samples underwent acidic along with basic liquid-liquid extraction with hexane: ethyl acetate (9:1, v/v). Chromatographic separation was carried out on a C18 column, with the mass spectrometer operated in multiple reaction monitoring mode and negative electrospray ionization. Seven patients with intractable epilepsy were dosed with various CBD-containing formulations and blood collected just before their daily morning administration. The method was validated following international guidelines in toxicology. Linear ranges were (ng/ml) 0.5-25 THC, 11-OH-THC, THCCOOH, 6-α-OH-CBD and 6-β-OH-CBD; 10-500 CBD and 7-OH-CBD; and 20-5000 7-COOH-CBD. 7-COOH-CBD was present in the highest concentrations, followed by 7-OH-CBD and CBD. This analytical method is useful for investigating CBD, THC and their major metabolites in epilepsy patients treated with CBD preparations employing a minimally invasive microsampling technique requiring only 30µL blood.

Results From a Proficiency Testing Pilot for Immunosuppressant Microsampling Assays.

Therapeutic drug monitoring (TDM) of immunosuppressive drugs is important for the prevention of allograft rejection in transplant patients. Several hospitals offer a microsampling service that provides patients the opportunity to sample a drop of blood from a fingerprick at home that can then be sent to the laboratory by mail. The aim of this study was to pilot an external quality control program. Fourteen laboratories from 7 countries participated (fully or partly) in 3 rounds of proficiency testing for the immunosuppressants tacrolimus, ciclosporin, everolimus, sirolimus, and mycophenolic acid. The microsampling devices included the following: Whatman 903 and DMPK-C, HemaXis, Mitra, and Capitainer-B. All assays were based on liquid chromatography with tandem mass spectrometry. In round 2, microsamples as well as liquid whole blood samples were sent, and 1 of these samples was a patient sample. Imprecision CV% values for the tacrolimus microsamples reported by individual laboratories ranged from 13.2% to 18.2%, 11.7%-16.3%, and 12.2%-18.6% for rounds 1, 2, and 3, respectively. For liquid whole blood (round 2), the imprecision CV% values ranged from 3.9%-4.9%. For the other immunosuppressants, the results were similar. A great variety in analytical procedures was observed, especially the extraction method. For the patient sample, the microsample results led to different clinical decisions compared with that of the whole blood sample. Immunosuppressant microsampling methods show great interlaboratory variation compared with whole blood methods. This variation can influence clinical decision-making. Thus, harmonization and standardization are needed. Proficiency testing should be performed regularly for laboratories that use immunosuppressant microsampling techniques in patient care.

Chemical and Isotopic Evaluation of a Microsampling Method using Laser Ablation and Membrane Filter

Microscale isotopic measurements in geological materials are becoming of significant importance in geochemistry. This study evaluated the potential of a new microsampling method called laser ablation coupled with filter (LAF) for precise isotopic measurements of small‐sized geological materials, compared with conventional micromilling techniques. We optimised the system to maximise the sample collection rate and minimise the extent of the contamination. Isotope ratios (87Sr/86Sr, 142Nd/144Nd, 143Nd/144Nd, 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb) of the glass reference material NIST SRM 610 collected using LAF were measured by thermal ionisation mass spectrometry, and no isotopic fractionation or blank effect was observed. This indicates that LAF can be applied for high‐precision isotope ratio measurement of these elements. Considering the total procedural blanks in LAF sampling, the minimum amounts required for high‐precision isotope measurement were 50, 2 and 20 ng for Sr, Nd and Pb, respectively. The LAF method has advantages over the conventional method. It also causes less damage in the test sample’s depth direction and can be applied to samples with complex shapes. It is expected therefore that the LAF sampling method will be applied to geology and other research fields that require microsampling.

Application of Solid-state Electrochemical Analysis in Ancient Ceramic Identification and Characterization: A Review

Background: Ceramics can reflect ancient technology and art, therefore, it has a very important position in archaeology. However, it is far from enough just to study the shape of pottery and porcelain. It is necessary to use advanced scientific and technological means to conduct a comprehensive analysis of pottery and porcelain, so as to study the information hidden deep in the remains of ceramic objects. Methods: The solid voltammetric method can be used to obtain information about the composition of materials used in ancient ceramics. This new method can be applied to insoluble solids for example, providing qualitative and quantitative information and structural information with little soluble solids. The method requires only ng-μg sample. Results: In this review, we first describe the development of solid-state voltammetric method and our work in this field. Then, we describe in detail the application of this method in archaeology, especially in the analysis of ceramics. Finally, we describe the analytical applications of other electrochemical techniques for ceramics analysis. Conclusion: Due to the low demand for samples and the high-cost performance of analytical instruments, this method has been widely studied in Europe. To sum up, we propose to establish a microsampling method for ancient ceramics. A new method for the protection of fine ancient ceramics by the suitable carrier and the fixation on the surface of the electrode. These improvements can enable solid-state electroanalytical chemistry technology to achieve more comprehensive and accurate quantitative analysis of ancient ceramics particles. We also propose the current challenges and future directions of solid-state electroanalytical chemistry.

Homogeneity assessment of the elemental composition of windshield glass by µ-XRF, LIBS and LA-ICP-MS analysis

This study evaluates the capability of μ-XRF and LIBS analyses to characterize the homogeneity (elemental variation) of glass compared to the LA-ICP-MS quantitative analysis method. Two premises in the forensic comparison of glass are that 1) the elemental composition across a single source (e.g., a pane) is homogeneous and 2) the elemental variation within a single source is much smaller than the elemental variation observed among different glass sources (different panes manufactured at different sites or different times). These assumptions are widely supported when using microsampling methods such as LA-ICP-MS; however, systematic homogeneity studies using μ-XRF and LIBS methods are unavailable. In this study, the variability of the elemental composition within 100 fragments from two different panes of the same windshield was characterized using chemical maps, and semi-quantitative data was used to compare fragments within and between the different panes. When comparing pieces within the same pane, the variability for most elements was less than 10% RSD for both μ-XRF and LIBS and less than 5% RSD for LA-ICP-MS. Comparison methods simulating casework situations in which one questioned fragment is compared to more than one known fragment resulted in better performance as the number of fragments of the known sample increased (to up to 4 fragments, 12–20 measurements). The results show the comparison criteria should be selected according to the instrument’s precision and sensitivity. Error rates below 3% were obtained for μ-XRF and LIBS when selecting the appropriate number of fragments, measurements, and comparison criterion.

Children of the abyss: Investigating the association between isotopic physiological stress and skeletal pathology in London during the Industrial Revolution

ObjectiveThis project sought to investigate whether an association may be observed between isotopic stress indicators and skeletal evidence of pathological conditions. MaterialsDeciduous and permanent teeth of 15 non-adults from two contemporaneous mid-19th century London burial grounds (City Bunhill, Lukin Street). Methodsδ13C and δ15N was measured in the incrementally sectioned dentine collagen. Isotopic profiles for each individual included death during tooth development. ResultsIndividuals with skeletal evidence of chronic pathological conditions (e.g., rickets, tuberculosis) exhibited raised δ15N values of 0.5–1.7‰ in the months prior to death. Isotopic change consistent with chronic physiological stress prior to death was also recorded in two individuals with no skeletal evidence of disease. An offset was observed between co-forming bone and dentine δ15N values in both populations, indicating that bone and dentine are not recording the same isotopic changes. ConclusionsIsotopic change consistent with chronic physiological stress was observed in both those with and without skeletal evidence of disease, suggesting that adaptation to chronic stress in childhood was not uncommon within these 19th century London populations. SignificanceChronic physiological stress prior to death may be seen in the incrementally sampled dentine of non-adults who die during tooth formation. LimitationsThe temporal resolution of current dentine micro-sampling methods may mask or minimise visibility of shorter-term periods of stress or dietary change. Suggestions for further researchFuture research should further explore the relationship between specific skeletal pathologies and isotopic evidence for stress.

Analysis of tamoxifen and its metabolites in dried blood spot and volumetric absorptive microsampling: comparison and clinical application

This research was conducted to develop the Dried Blood Spot (DBS) and Volumetric Absorptive Microsampling (VAMS) method in the analysis of Tamoxifen (TAM) and its metabolites endoxifen (END), 4-hydroxytamoxifen (4-HT), and N-desmethyltamoxifen (NDT) using Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). This method was then applied to monitor TAM and its metabolites in breast cancer patients. The UPLC-MS/MS method was developed and validated with propranolol as the internal standard. The recovery and matrix effects on DBS and VAMS were investigated. The validation requirements were fulfilled by the methodology of analysis and sample preparation described in this study. Both VAMS and DBS extraction recoveries were satisfactory, with low variability. Extraction recovery in the VAMS sample was found to be slightly higher than in the DBS sample. Sample stability in DBS and VAMS was demonstrated for up to 2 months. Both of these methods were successfully applied for the analysis of TAM and metabolites in clinical patients. The mean concentrations obtained from the two methods were not significantly different.

Simultaneous Determination of As, Bi, Sb, Se, Te, Hg, Pb and Sn by Small-Sized Electrothermal Vaporization Capacitively Coupled Plasma Microtorch Optical Emission Spectrometry Using Direct Liquid Microsampling.

The simultaneous determination of chemical vapor-generating elements involving derivatization is difficult even by inductively coupled plasma optical emission spectrometry or mass spectrometry. This study proposes a new direct liquid microsampling method for the simultaneous determination of As, Bi, Se, Te, Hg, Pb, and Sn, using a fully miniaturized set-up based on electrothermal vaporization capacitively coupled plasma microtorch optical emission spectrometry. The method is cost-effective, free from non-spectral interference, and easy to run by avoiding derivatization. The method involves the vaporization of analytes from the 10 µL sample and recording of episodic spectra generated in low-power (15 W) and low-Ar consumption (150 mL min−1) plasma microtorch interfaced with low-resolution microspectrometers. Selective vaporization at 1300 °C ensured the avoidance of non-spectral effects and allowed the use of external calibration. Several spectral lines for each element even in the range 180–210 nm could be selected. Generally, this spectral range is examined with large-scale instrumentation. Even in the absence of derivatization, the obtained detection limits were low (0.02–0.75 mg kg−1) and allowed analysis of environmental samples, such as cave and river sediments. The recovery was in the range of 86–116%, and the accuracy was better than 10%. The method is of general interest and could be implemented on any miniaturized or classical laboratory spectrometric instrumentation.