scholarly journals Measurement of Dabigatran Concentration Using Finger Prick Dried Blood Spot Sample Collection

2021 ◽  
Vol 12 ◽  
Author(s):  
Shin-Yi Lin ◽  
Yu-Fong Peng ◽  
Chih-Fen Huang ◽  
Ching-Hua Kuo ◽  
Sung-Chun Tang ◽  
...  
Keyword(s):  
High Performance ◽  
Internal Standard ◽  
Dried Blood Spot ◽  
Altman Analysis ◽  
Sample Collection ◽  
Bland Altman Analysis ◽  
Clinical Scenarios ◽  
Deming Regression ◽  
Finger Prick ◽  
Blood Spot

Background and Purpose: Real-world laboratory monitoring of dabigatran activity is challenging. The purpose of the present study was to demonstrate the feasibility and accuracy of finger prick sampling with dried blood spot (fpDBS) cards in measuring the dabigatran concentration.Material and Methods: Patients >20 years of age with atrial fibrillation and receiving dabigatran therapy for more than 7 days were included in the study. Peak and trough dabigatran concentrations were collected by simultaneous finger prick and venous puncture. The dabigatran concentration was measured by ultra-high performance liquid chromatography with tandem mass spectrometry. Our previously developed post-column infused internal standard (PCI-IS) method was applied to estimate the blood spot volume on fpDBS and to calibrate the drug concentration. Deming regression was used to analyze the correlation between dabigatran concentration on fpDBS cards and in plasma samples, followed by Bland–Altman analysis to compare the bias between two sampling techniques.Results: A total of 33 patients were enrolled and contributed 66 plasma and 55 fpDBS dabigatran samples. The average patient age was 74.6 ± 7.9 years, mean creatinine clearance 58.1 ± 18.3 mL/min, and CHA2DS2-VASc score 3.5 ± 1.6 points. The dabigatran concentration ranged from 41.8–1421.7 ng/mL. The plasma and DBS dabigatran concentrations correlated well (r = 0.98), and the conversion factor for fpDBS to plasma dabigatran concentration was 1.28. The Bland–Altman analysis showed that 94.5% of the fpDBS-predicted concentration fell within 20% of bias.Conclusions: The study showed that fpDBS measurement of dabigatran concentration is reliable and can be applied in clinical scenarios.

scholarly journals Fluispotter, a novel automated and wearable device for accurate volume serial dried blood spot sampling

Bioanalysis ◽  
2020 ◽  
Author(s):  
Khem Bahadur Adhikari ◽  
Morten Rohde ◽  
Sten Velschow ◽  
Ulla Feldt-Rasmussen ◽  
Jesper Johannesen ◽  
...  
Keyword(s):  
Blood Volume ◽  
Plasma Cortisol ◽  
High Accuracy ◽  
Dried Blood Spot ◽  
Altman Analysis ◽  
Accuracy And Precision ◽  
Serial Sampling ◽  
Deming Regression ◽  
Blood Spot ◽  
Good Agreement

Aim: A novel automated serial dried blood spot (DBS) sampler, ‘Fluispotter’, was tested for its sampling performance. Materials & methods: An LC–MS/MS method was developed for the analysis of cortisol in DBS samples serially spotted by Fluispotter. The cortisol concentrations in 148 paired DBS and plasma samples were compared across a hematocrit (HCT) range of 22–55%. Results: The interassay accuracy and precision were <10%. Overall assay bias was negligible across the HCTs tested when analyzing the whole-spot DBS samples. The accuracy and precision of the blood volume in 10 μl DBS samples spotted by Fluispotters and micropipettes were within 3%. Deming regression and Bland-Altman analysis showed a good agreement of DBS-predicted and measured plasma cortisol. Conclusion: The Fluispotter performed serial sampling with high accuracy and precision of the sample blood volume.

scholarly journals Metabolic profiles derived from residual blood spot samples: A longitudinal analysis

2018 ◽  
Vol 2 ◽  
pp. 28 ◽  
Author(s):  
Malia S.Q. Murphy ◽  
Steven Hawken ◽  
Wei Cheng ◽  
Lindsay A. Wilson ◽  
Monica Lamoureux ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Gestational Age ◽  
High Performance ◽  
Intraclass Correlation ◽  
Estimation Algorithm ◽  
Dried Blood Spot ◽  
Sample Collection ◽  
Secondary Use ◽  
Blood Spot ◽  
Age Estimates

Background: Secondary use of newborn screening dried blood spot samples include use for biomedical or epidemiological research. However, the effects of storage conditions on archival samples requires further examination. The objective of this study was to determine the utility of residual newborn samples for deriving reliable metabolic gestational age estimates. Methods: Residual newborn dried blood spot samples that had been stored for 2-, 4-, 6-, or 12-months in temperature controlled (21°C) conditions were re-analyzed for the full panel of newborn screening analytes offered by a provincial newborn screening lab in Ottawa, Canada. Data from re-analyzed samples were compared to corresponding baseline newborn screening values for absolute agreement, and Pearson and intraclass correlation. Performance of a gestational age estimation algorithm originally developed from baseline newborn screening values was then validated on data derived from stored samples. Results: A total of 307 samples were used for this study. 17-hydroxyprogesterone and newborn hemoglobin profiles measured by immunoassay and high-performance liquid chromatography, respectively, were among the most stable markers across all time points of analysis. Acylcarnitines exhibited the greatest degree of variation in stability upon repeat measurement. The largest shifts in newborn analyte profiles and the poorest performance of metabolic gestational age algorithms were observed when samples were analyzed 12-months after sample collection. Conclusions: Duration of sample storage, independent of temperature and humidity, affects newborn screening profiles and gestational age estimates derived from metabolic gestational dating algorithms. When considering use of dried blood spot samples either for clinical or research purposes, care should be taken when interpreting data stemming from secondary use.

Volumetric dried blood spot sampling by coordinated burst action of hydrophobic burst valves

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Dries Vloemans ◽  
Lorenz Van Hileghem ◽  
Wannes Verbist ◽  
Debby Thomas ◽  
Francesco Dal Dosso ◽  
...  
Keyword(s):  
Dried Blood Spot ◽  
Sample Collection ◽  
Collection Method ◽  
Blood Spot

Dried blood spot (DBS) sampling by finger-pricking has recently gained a lot of interest as alternative sample collection method. The reduced invasiveness, requirement of lower sample volumes and suitability for...

Candidate reference method for determination of vitamin D from dried blood spot samples

2020 ◽  
Vol 58 (5) ◽  
pp. 817-827 ◽  
Author(s):  
Rosita Zakaria ◽  
Katrina J. Allen ◽  
Jennifer J. Koplin ◽  
Peter Roche ◽  
Ronda F. Greaves
Keyword(s):  
Vitamin D ◽  
Internal Standard ◽  
Reference Method ◽  
Population Level ◽  
Population Based ◽  
Dried Blood Spot ◽  
Coefficient Of Determination ◽  
Plasma Vitamin ◽  
Blood Spot

AbstractBackgroundThe current millennium has seen an explosion in vitamin D testing with the overarching aim of requests to clinically stratify patients as replete or deficient in vitamin D. At a population level, dried blood spot (DBS) sampling offers a less invasive and more practical application for assessment of vitamin D status. We have therefore aimed to develop a sensitive and robust DBS vitamin D method that is traceable to serum for use in population-based studies.MethodsBlood spots, calibrators and controls were prepared by punching a 3.2 mm DBS from filter paper and placed into a 96-well micro-plate. The DBS disk was eluted with a combination of water-methanol and internal standard (ISTD) solution followed by supported-liquid extraction and derivatisation. The extract was analysed by liquid-chromatography tandem-mass spectrometry in positive electrospray-ionisation mode with 732.5 > 673.4 and 738.4 > 679.4 m/z ion-transitions for derivatised vitamin D and the ISTD, respectively. Vitamin D results were made traceable to the National Institute of Standards and Technology reference material through the inclusion of Chromsystems vitamin D calibrators.Results25-Hydroxy-vitamin D3 and its related ISTD were detected at a retention time of 7 min. The seven-point calibration-curve consistently demonstrated a coefficient of determination of 0.99 with an experimentally determined reportable range of 0.5–376 nmol/L. Method validation studies using DBS samples demonstrated 12.9% between-assay imprecision at 45 nmol/L, 84% average recovery and high correlation with plasma vitamin D (correlation coefficient = 0.86).ConclusionsWe have successfully developed an analytical method for vitamin D quantitation from DBSs which will be applied to our population-based vitamin D research study. This approach improves traceability of DBS results and potentially could be used broadly for other DBS measurands that require comparison to serum/plasma for their interpretation.

scholarly journals SIMPLE AND RAPID METHOD FOR THE SIMULTANEOUS ANALYSIS OF TAMOXIFEN, ENDOXIFEN, AND 4-HYDROXYTAMOXIFEN IN DRIED BLOOD SPOT USING LIQUID CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY

2020 ◽  
pp. 112-120
Author(s):  
BAITHA PALANGGATAN MAGGADANI ◽  
YAHDIANA HARAHAP ◽  
HARMITA ◽  
SAMUEL J. HARYONO ◽  
TESANIKA RIBKA JOULIN SITORUS
Keyword(s):  
Formic Acid ◽  
Mobile Phase ◽  
Internal Standard ◽  
Cancer Recurrence ◽  
Dried Blood Spot ◽  
Active Metabolites ◽  
Drying Time ◽  
Liquid Chromatography Tandem Mass ◽  
Blood Spot ◽  
Spot Volume

Objective: Tamoxifen (TAM) is a hormonal therapy that is clinically proven to reduce breast cancer recurrence by blocking estrogen receptor, mainly through its active metabolites, 4-hydroxytamoxifen (4HT) and endoxifen (END), which have a higher affinity to ER than TAM itself. The objective of the present study was to develop and validate simple and rapid LC-MS/MS method for analysis TAM and its metabolites simultaneously in dried blood spot (DBS) sample for monitoring studies purposes. Methods: Optimization was done by evaluating several parameters that affect the efficiency of DBS preparation, such as blood spot volume, drying time and extraction method from the DBS paper. The effectiveness of chromatographic conditions was also optimized by varying flow rate, mobile phase combination and gradient. Clomiphene was used as the internal standard. Results: The result showed that preparation of 20 µl blood spot volume with 120 min of drying time and 25 min of extraction time using 1 ml methanol was the most efficient condition and also fulfilled recovery and matrix effect requirement according to FDA and EMA guidelines. The separation was performed on UPLC Class BEH C18 using formic acid 0.1%-formic acid 0.1% in acetonitrile (35:65) as the mobile phase in isocratic mode at 0.25 ml/min with a total analysis time of 4 min. Conclusion: This method has successfully fulfilled all validation requirements referring to EMA and FDA guidelines.

scholarly journals Assessment of a dried blood spot C-reactive protein method to identify disease flares in rheumatoid arthritis patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Leon G. D’Cruz ◽  
Kevin G. McEleney ◽  
Chris Cochrane ◽  
Kyle B. C. Tan ◽  
Priyank Shukla ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Damage ◽  
Reference Method ◽  
Detection Sensitivity ◽  
Dried Blood Spot ◽  
Enzyme Linked Immunosorbent Assay ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Deming Regression ◽  
Blood Spot

AbstractRheumatoid arthritis (RA) is characterised by painful, stiff and swollen joints. RA features sporadic ‘flares’ or inflammatory episodes—mostly occurring outside clinics—where symptoms worsen and plasma C-reactive protein (CRP) becomes elevated. Poor control of inflammation results in higher rates of irreversible joint damage, increased disability, and poorer quality of life. Flares need to be accurately identified and managed. A method comparison study was designed to assess agreement between CRP values obtained by dried blood spot (DBS) versus conventional venepuncture sampling. The ability of a weekly DBS sampling and CRP test regime to detect flare outside the clinic was also assessed. Matched venepuncture and finger lancet DBS samples were collected from n = 100 RA patients with active disease at baseline and 6 weeks (NCT02809547). A subset of n = 30 RA patients submitted weekly DBS samples over the study period. Patient demographics, including self-reported flares were recorded. DBS sample CRP measurements were made by enzyme-linked immunosorbent assay, and venepuncture samples by a reference immunoturbometric assay. Data was compared between sample types by Bland–Altman and weighted Deming regression analyses. Flare detection sensitivity and specificity were compared between ‘minimal’ baseline and 6 week sample CRP data and the ‘continuous’ weekly CRP data. Baseline DBS ELISA assay CRP measures yielded a mean positive bias of 2.693 ± 8.640 (95% limits of agreement − 14.24 to 19.63%), when compared to reference assay data. Deming regression revealed good agreement between the DBS ELISA method and reference assay data, with baseline data slope of 0.978 and intercept -0.153. The specificity of ‘continuous’ area under the curve (AUC) CRP data (72.7%) to identify flares, was greater than ‘minimal’ AUC CRP data (54.5%). This study indicates reasonable agreement between DBS and the reference method, especially at low to mid-range CRP values. Importantly, longitudinal CRP measurement in RA patients helps to clearly identify flare and thus could assist in remote monitoring strategies and may facilitate timely therapeutic intervention.Trial registration: The Remote Arthritis Disease Activity MonitoR (RADAR) study was registered on 22/06/2016 at ClinicalTrials.gov Identifier: NCT02809547. https://clinicaltrials.gov/ct2/show/NCT02809547.

Validation and clinical application of dried blood spot assay for quantitative assessment of edoxaban in healthy adults

Bioanalysis ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 393-407
Author(s):  
Ling He ◽  
Roohi Gajee ◽  
Raj Mangaraj ◽  
Michael P Waldron ◽  
Karen S Brown
Keyword(s):  
Healthy Subjects ◽  
Quantitative Assessment ◽  
Dried Blood Spot ◽  
Plasma Samples ◽  
Open Label ◽  
Finger Prick ◽  
Incurred Sample Reanalysis ◽  
Alternative Methodology ◽  
Blood Spot ◽  
Sampling Approach

Aim: Dried blood spot (DBS) is a sampling approach that offers several advantages over plasma and whole blood (WB) sampling, but several factors, such as hematocrit and temperature, can adversely affect quantitation. Methodology & results: In an open-label, three-way crossover study in healthy subjects, we explored the correlation between DBS, WB and plasma samples, and between DBS samples from finger-prick and venipuncture blood for measuring edoxaban and its metabolite M-4 using LC–MS/MS. The methods were validated comprehensively. The incurred sample reanalysis experiments demonstrated quantitation reproducibility in all three matrices. Overall, there was a good correlation (near perfect concordance for edoxaban) among plasma, WB and DBS measurements. M-4 concentrations in DBS and WB were lower than in plasma. Conclusion: These results indicate using DBS may be used as an alternative methodology to measure edoxaban pharmacokinetics.

scholarly journals Performance of StatSensor Point-of-Care Device for Measuring Creatinine in Patients With Chronic Kidney Disease and Postkidney Transplantation

2020 ◽  
Vol 7 ◽  
pp. 205435812097071
Author(s):  
Melissa Nataatmadja ◽  
Angela W. S. Fung ◽  
Beryl Jacobson ◽  
Jack Ferera ◽  
Eva Bernstein ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Whole Blood ◽  
Point Of Care ◽  
Reference Method ◽  
Plasma Creatinine ◽  
Altman Analysis ◽  
Bland Altman Analysis ◽  
Deming Regression ◽  
Ckd Stage

Background: The StatSensor is a point-of-care device which measures creatinine in capillary whole blood. Previous studies reported an underestimation of the creatinine measurements at high creatinine concentrations and were performed in the prestandardization era for creatinine. Objective: This accuracy-based study evaluates the use of this device in kidney-transplanted patients and those with chronic kidney disease (CKD). Design: Cross-sectional diagnostic accuracy study. Setting: Nephrology outpatient clinic in an urban tertiary center. Participants: Adults with CKD or a functioning kidney transplant. Measurements: Duplicate StatSensor creatinine measurements were performed on capillary whole blood samples collected by direct fingerstick and SAFE-T-FILL collection device. Results were compared with simultaneous venous blood sampling for serum and plasma creatinine measured by an enzymatic method on the Roche Integra 400 mainframe analyzer with traceability to the ID-GC-MS (isotope dilution gas chromatography mass spectrometry) reference method. Methods: Deming regression, Pearson correlation coefficient, and Bland-Altman analysis were used to assess accuracy and comparability between capillary whole blood measured by StatSensor and plasma creatinine measured by routine analyzer with traceability to the reference method. Estimated glomerular filtration (eGFR) rates were calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and concordance with Kidney Disease Improving Global Outcomes (KDIGO) CKD stage classification was evaluated. Results: There were 60 participants (mean age = 61.9 ± 15.0 years, 55% men, 33% transplant, mean plasma creatinine = 137 ± 59 µmol/L). Bland-Altman analysis indicated a positive mean bias of 12.7 µmol/L between StatSensor fingerstick creatinine measurement and plasma creatinine. Comparison of eGFR (CKD-EPI) calculated from the StatSensor fingerstick creatinine versus plasma creatinine showed misclassification across all KDIGO CKD stages. Postanalytical correction of the bias did not improve misclassifications. The use of mean of duplicate StatSensor creatinine results did not improve performance compared with the use of singlet results. Limitations: Single center, limited participant numbers. Conclusions: The results of our study suggest that the limiting characteristics of the StatSensor device are not only bias, but also imprecision. The level of imprecision observed may influence clinical decision-making and limit the usefulness of StatSensor as a CKD screening tool. If choosing to utilize it for either screening for or monitoring CKD, it is essential that clinicians understand the limitations of point-of-care devices and apply this knowledge to test interpretation.

scholarly journals Clinical Evaluation of a Dried Blood Spot Assay for Atazanavir

2010 ◽  
Vol 54 (10) ◽  
pp. 4124-4128 ◽  
Author(s):  
Trevor Van Schooneveld ◽  
Susan Swindells ◽  
Sarah R. Nelson ◽  
Brian L. Robbins ◽  
Ryan Moore ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Plasma Concentrations ◽  
Reversed Phase ◽  
Hiv Protease ◽  
Dried Blood Spot ◽  
Hiv Protease Inhibitors ◽  
Hiv Rna ◽  
Drug Concentrations ◽  
Blood Spot

ABSTRACT Current procedures for obtaining and measuring plasma concentrations of HIV protease inhibitors (PIs) are technically challenging. Dried blood spot (DBS) assays offer a way to overcome many of the obstacles. We sought to develop a DBS assay for quantitation of the PI atazanavir (ATV) and to compare this method with a previously validated plasma assay. We prospectively enrolled 48 patients with well-controlled HIV disease who had been on ATV for at least 7 days. ATV was quantified from plasma by use of high-performance liquid chromatography (HPLC). A reversed-phase ultrahigh-performance liquid chromatography (UPLC) assay was utilized for DBS samples. The concentrations of ATV quantified in a DBS matrix showed very strong agreement with those measured in plasma (r 2 = 0.988). The mean difference in ATV concentration between the two methods was −10.8% (95% confidence interval [95% CI], −7.65% to −13.95%), indicating that the DBS method has a slight negative bias. A majority (97.8%) of the differences in concentration between the two assays fell within ±2 standard deviations. ATV concentrations were lower in subjects who had detectable HIV RNA in plasma (mean, 543 ng/ml) than in those with HIV RNA of <50 copies/ml (mean, 1,582 ng/ml) (P = 0.03, Wilcoxon rank-sum test). In conclusion, our study demonstrated that ATV quantitation in a DBS matrix is feasible and accurate. DBS use offers a convenient alternative for measuring plasma concentrations of ATV and may have utility in monitoring of drug concentrations in clinical practice and in future studies.

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