Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Antipsychotics: Drawbacks of Its Clinical Application

Kloosterboer, Sanne; Winter, Brenda C M de; Bahmany, Soma; Al-Hassany, Linda; Dekker, A.; Dieleman, Gwen; Gelder, Teun van; Dierckx, Bram; Koch, Birgit C. P.

doi:10.1097/ftd.0000000000000502

Cited by 39 publications

(48 citation statements)

References 20 publications

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“…Deming regression analyses were then performed to assess any constant and/or proportional bias between plasma and DBS AHD/[metabolite] measurements. 12 A proportional bias was obtained if the 95% confidence interval (95%-CI) of the regression line slope did not contain 1. When the 95% CI of the regression line intercept did not contain 0, the data were considered to have a constant bias.…”

Section: Clinical Validationmentioning

confidence: 99%

“…It was therefore necessary to validate this method extensively, to observe for the similarities/equality in drug concentrations, compared with plasma-only measurements. Although the DBS method has been used to accurately measure immunosuppressive and antipsychotic drug concentrations, [12][13][14] it has not been validated for AHD measurements. [15][16][17] In this study, we developed (following analytical validation) and clinically validated a DBS method for 8 commonly used AHDs from the 4 most frequently prescribed drug classes, by qualifying and quantifying the AHD and active metabolite (displayed within [brackets]) concentrations, using UHPLC-MS/MS.…”

Section: Introductionmentioning

confidence: 99%

“…7 DBS assay validation was performed following the FDA/EMA guidelines on bioanalytical method validation, 18,19 and the concept guidelines of the alternative sampling committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDCMT), and as previously described. 12,20,21…”

Section: Introductionmentioning

confidence: 99%

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Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites

Peeters¹,

Feyz

Hameli³

et al. 2020

Therapeutic Drug Monitoring

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Background: Drug nonadherence is one of the major challenges faced by resistant hypertension patients, and identification of this problem is needed for optimizing pharmacotherapy. Dried blood spot (DBS) sampling is a minimally invasive method designed to detect and determine the degree of nonadherence. In this study, a DBS method for qualifying 8 antihypertensive drugs (AHDs) and 4 active metabolites was developed and validated using ultra highperformance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Method: The DBS assay was validated analytically and clinically, in accordance with FDA requirements. Analytical validation was accomplished using UHPLC-MS/MS. For clinical validation, paired peak and trough levels of DBS and plasma samples were simultaneously collected and comparatively analyzed using Deming regression and Bland-Altman analyses. All concentrations below the set lower limit were excluded. Deming regression analysis was used to predict comparison bias between the collected plasma and DBS samples, with DBS concentrations corrected accordingly. Results: The UHPLC-MS/MS method for simultaneously measuring 8 AHDs and their metabolites in DBS, was successfully validated. With Deming regression no bias was observed in N = 1; constant bias was seen in N = 6 and proportional bias in N = 11 of the AHDs and metabolites. After correction for bias, only one metabolite (canrenone) met the 20% acceptance limit for quantification, after Bland-Altman analyses. In addition, amlodipine, valsartan, and [enalaprilate] met the 25% acceptance limit. Conclusions: A novel DBS assay for simultaneously qualifying and quantifying 8 AHDs and their metabolites, has been successfully developed and validated. The DBS assay is therefore a suitable method to detect drug nonadherence. However, with the exception of canrenone, the interchangeable use of plasma and DBS sampling to interpret drug quantities should be avoided.

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Section: Clinical Validationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites

Peeters¹,

Feyz

Hameli³

et al. 2020

Therapeutic Drug Monitoring

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“…At the time of the check-up, blood-drug concentrations and creatinine levels will be available for the clinician and the patient. Current challenges of DBS implementation include the influence of the hematocrit and logistical hurdles [9,13,17,18]. Although DBS analytical methods can meet the required analytical standards, analysis of clinically collected samples does not always result in sufficient agreement between the standard (venous) method and the novel fingerprick DBS method [17].…”

Section: Introductionmentioning

confidence: 99%

“…Current challenges of DBS implementation include the influence of the hematocrit and logistical hurdles [9,13,17,18]. Although DBS analytical methods can meet the required analytical standards, analysis of clinically collected samples does not always result in sufficient agreement between the standard (venous) method and the novel fingerprick DBS method [17]. Therefore, a clinical validation study showing interchangeability between DBS and venous sampling is required before clinical application [18].…”

Section: Introductionmentioning

confidence: 99%

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Veenhof

Koster²,

Alffenaar

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. Methods A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. Two validation limits were pre-defined: limits of analytical acceptance were set at >67% of all paired samples within 20% of the mean of both samples and limits of clinical relevance were set in a multidisciplinary team at >80% of all paired samples within 15% of the mean of both samples. Results For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72–1.02) and 0.96 (95% CI 0.84–1.06), respectively. Only everolimus showed a significant constant bias of 4%. For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively). Conclusions Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. However, if the clinical setting is compatible with less strict limits for clinical relevance, this DBS method is suitable for clinical application.

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Development and validation of an LC–MS/MS method for relevant drugs in epilepsy patients using dried blood spots

Möller

Held

Klimpel

et al. 2021

Biomedical Chromatography

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Epilepsy is one of the most common diseases of the central nervous system globally. To ensure the correct dosage of antiepileptic treatment, it is helpful to check the blood levels of the administered substances regularly. The analysis of the capillary dried blood samples provides a promising and less‐invasive alternative to venous blood collection. Therefore, the aim of the present study was to develop an LC–MS method for the quantification of 22 commonly used drugs in patients with an epileptic syndrome and 5 drug metabolites in one dried blood spot (DBS). The calibration ranges were selected in such a way that the therapeutic reference ranges in serum for the respective substances were completely covered. The analytical validation was successfully performed according to relevant guidelines with a consideration of requirements for DBS analysis. Proof of concept of the developed method was obtained by the analysis of DBSs from 282 authentic leftover ethylenediaminetetraacetic acid blood samples, which were compared with the corresponding serum concentrations. Altogether, the results show a dependency on the blood/plasma (b/p) ratios of the respective analytes so that for drugs with b/p ratios close to one, for example, lacosamide, levetiracetam, brivaracetam, and sertraline, a good accordance was observed.

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Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Antipsychotics: Drawbacks of Its Clinical Application

Cited by 39 publications

References 20 publications

Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites

Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Development and validation of an LC–MS/MS method for relevant drugs in epilepsy patients using dried blood spots

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