| 1. |
- Lenk, Gabriel, 1986-, et al.
(författare)
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A Disposable Chip Enabling Metering In Dried Blood Spot Sampling
- 2013
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Konferensbidrag (refereegranskat)abstract
- This work presents a disposable chip for metering and transferring an exactly defined liquid volume into a paper matrix by capillary filling and emptying of a microchannel together with self-actuated dissolvable valves. Once a liquid droplet of 20-50 μl is applied to the chip, a volume of 1 μl is automatically metered, separated from the applied volume and subsequently transferred into conventional Whatman 903 paper used in Dried Blood Spot (DBS) sampling. The presented concept allows accurate volume metering for lateral flow devices and is here designed to the specific purpose of metering blood spots for DBS analysis. The material costs for each chip are below 0.04 €.
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| 2. |
- Lenk, Gabriel, 1986-, et al.
(författare)
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A Disposable Chip for the Collection of Quantitative Dried Blood Spot Samples
- 2014
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Konferensbidrag (refereegranskat)abstract
- This work presents a disposable chip for metering and transferring an exactly defined liquid volume into a paper matrix using self-actuated dissolvable valves. Once a liquid droplet of 20-50 μl is applied to the chip, a volume of 1 μl is automatically metered, separated from the applied volume and subsequently transferred into conventional Whatman 903 paper used in Dried Blood Spot (DBS) sampling.
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| 3. |
- Lenk, Gabriel, et al.
(författare)
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A disposable sampling device to collect volume-measured DBS directly from a fingerprick onto DBS paper
- 2015
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. ; 7:16, s. 2085-2094
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Tidskriftsartikel (refereegranskat)abstract
- Background: DBS samples collected from a fingerprick typically vary in volume and homogeneity and hence make an accurate quantitative analysis of DBS samples difficult. Results: We report a prototype which first defines a precise liquid volume and subsequently stores it to a conventional DBS matrix. Liquid volumes of 2.2 mu l +/- 7.1% (n = 21) for deionized water and 6.1 mu l +/- 8.8% (n = 15) for whole blood have been successfully metered and stored in DBS paper. Conclusion: The new method of collecting a defined volume of blood by DBS sampling has the potential to reduce assay bias for the quantitative evaluation of DBS samples while maintaining the simplicity of conventional DBS sampling.
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| 4. |
- Linder, Camilla, et al.
(författare)
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Dried Blood Spot Self-Sampling by Guardians of Children With Epilepsy Is Feasible : Comparison With Plasma for Multiple Antiepileptic Drugs
- 2019
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Ingår i: Therapeutic Drug Monitoring. - : Lippincott Williams & Wilkins. - 0163-4356 .- 1536-3694. ; 41:4, s. 509-518
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dried blood spot (DBS) is an attractive matrix alternative to plasma for the measurement of antiepileptic drug concentrations with the possibility of self-sampling at home. The aim of this study was to evaluate whether DBS concentrations from a children population could be used as an alternative to plasma concentrations in a clinical routine laboratory.METHODS: Children with epilepsy using carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA) had capillary blood collected for routine plasma analysis. DBS samples were collected by guardians or nurses, and the quality of sampling was compared between the groups. DBS samples were analyzed with liquid chromatography-tandem mass spectrometry methods and plasma samples with immunochemical methods. In the comparison between DBS and plasma concentrations, previously analyzed sample data were pooled with data in this study and resulted in 190 comparison pairs. A bioanalytical cross-validation according to European Medicines Agency was performed. Clinicians evaluated the results to understand if a DBS concentration was linked to a different clinical dose recommendation for the patient in comparison with plasma concentrations.RESULTS: Comparison of DBS sample quality showed that 2.3% of the capillary DBS collected by guardians were rejected and 8.0% of the capillary DBS collected by nurses. For DBS, a conversion factor of 0.85 for CBZ and 1.65 for VPA was applied for the comparison with plasma. LTG and LEV results were directly comparable. In the cross-validation, 88% of CBZ, 75% of LTG, 74% of LEV, and 94% of VPA comparisons were within 20% of the difference of the mean, although LEV had a few major differences (+31% to -40%). In 4 of the 190 comparisons, the clinical evaluation indicated a risk of conflicting decisions regarding the need for dose adjustment when using DBS concentrations. However, the risk of negative patient outcomes was considered negligible.CONCLUSIONS: Our study demonstrates that a combination of bioanalytical cross-validation and clinical evaluation is an effective way to describe the applicability of DBS as an alternative to plasma, taking into account how therapeutic drug monitoring is used in specific patient groups. For LTG, converted CBZ and VPA, DBS is a feasible alternative for self-sampling at home. DBS for LEV can only be recommended for nonadherence queries due to the high variability of the plasma/DBS concentration ratios.
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| 5. |
- Niward, Katarina, et al.
(författare)
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Distribution of plasma concentrations of first-line anti-TB drugs and individual MICs: a prospective cohort study in a low endemic setting
- 2018
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 73:10, s. 2838-2845
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Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic drug monitoring (TDM) could improve current TB treatment, but few studies have reported pharmacokinetic data together with MICs. Objectives: To investigate plasma concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol along with MICs. Methods: Drug concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol were analysed pre-dose and 2, 4 and 6 h after drug intake at week 2 in 31 TB patients and MICs in BACTEC 960 MGIT were determined at baseline. The highest plasma concentrations at 2, 4 and 6 h post-dose (C-high) were determined, as well as estimates of C-high/MIC and area under the concentration-time curve (AUC(0-6))/MIC including the corresponding ratios based on calculated free-drug concentrations. This trial was registered at www.clinicaltrials.gov (NCT02042261). Results: After 2 weeks of treatment, the median C-high values for rifampicin, isoniazid, pyrazinamide and ethambutol were 10.0, 5.3, 41.1 and 3.3 mg/L respectively. Lower than recommended drug concentrations were detected in 42% of the patients for rifampicin (amp;lt;8 mg/L), 19% for isoniazid (amp;lt;3 mg/L), 27% for pyrazinamide (amp;lt;35 mg/L) and 16% for ethambutol (amp;lt;2 mg/L). The median Chigh/MIC values for rifampicin, isoniazid, pyrazinamide and ethambutol were 164, 128, 1.3 and 2.5, respectively, whereas the AUC(0-6)/MIC was 636 (range 156-2759) for rifampicin and 351 (range 72-895) for isoniazid. Conclusions: We report low levels of first-line TB drugs in 16%-42% of patients, in particular for rifampicin. There was a wide distribution of the ratios between drug exposures and MICs. The future use of MIC determinations in TDM is dependent on the development of a reference method and clinically validated pharmacokinetic/pharmacodynamic targets.
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| 6. |
- Said, Rana, et al.
(författare)
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Determination of four immunosuppressive drugs in whole blood using meps and lc ms/ms allowing automated sample work up and analysis
- 2012
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 897, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- In treatment with immunosuppressive drugs, monitoring of blood drug concentration is needed. The aim of this work was to explore micro extraction by packed sorbent (MEPS) as a possible on-line sample preparation method in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantification of cyclosporine, everolimus, sirolimus and tacrolimus in whole blood. An automated on-line MEPS system connected with a LC-MS/MS instrument was set up. A C-8 sorbent was used for the MEPS extraction. Subsequent analysis was performed with a gradient LC system. The adduct ions [M + NH4](+) of the analytes were monitored in SRM mode for quantification. Ascomycin and cyclosporine D were used as internal standards. The chromatographic run time 2.5 min and the quantification ranges were 3-1500 ng/mL (r(2) >= 0.999, n = 6) for cyclosporine and 0.5-50 ng/mL for everolimus, sirolimus and tacrolimus (r(2) >= 0.998. 0.994 and 0.993, respectively, n = 6). Precision and accuracy were documented at three levels. Accuracy results were between 102% and 109% with precision between 2% and 13% and carry over < 0.02%. Matrix effects were characterized and found to be below 20%. The quantifications obtained were in agreement with a reference LC-MS/MS method based on protein precipitation, and results obtained from external proficiency test samples compared with the mean of all other LC-mass spectrometry methods showed good agreement. This method provides an accurate, precise and automated procedure that can be applied for therapeutic drug monitoring of immunosuppressive drugs in clinical laboratories equipped with LC-MS/MS.
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| 7. |
- Yasinska, Valentyna, et al.
(författare)
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Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months.Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.
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