Dried Blood Spot Measurement of Tacrolimus Is Promising for Patient Monitoring

Hoogtanders, K.; Heijden, J. van der; Christiaans, Maarten H. L.; Plas, Afke van de; Hooff, Johannes van; Stolk, L. M. L.

doi:10.1097/01.tp.0000250730.30715.63

Cited by 58 publications

(41 citation statements)

References 6 publications

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“…Recently, a method for measurement of tacrolimus level, based on DBS and high-performance liquid chromatography tandem-mass spectrometry (HPLC-MS), has been developed [5]. Preliminary results showed that DBS is promising for routine tacrolimus monitoring of stable renal transplant recipients [6].…”

Section: Introductionmentioning

confidence: 99%

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation

et al. 2007

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Section: Introductionmentioning

confidence: 99%

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation

et al. 2007

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“…In comparison with previously described LC-MS/MS assays to quantify tacrolimus in dried bloods spots [29][30][31][32][33][34]36,39,41,42 , the present assay matches or exceeds their performance in terms of lower limit of quantification, extraction recovery, accuracy and precision while avoiding potentially risky concepts such as one-step protein precipitation procedures and ultra-short chromatography times, which usually give acceptable results during the validation based on blood samples from healthy individuals. However, transplant patients are a highly complex group of patients who have diseases that affect the composition of blood and who take multiple medications.…”

Section: Discussionmentioning

confidence: 99%

“…After a simple finger stick the patient collects a blood drop on a special filter paper card and after the blood spot has dried, it can be mailed to a central laboratory for analysis of tacrolimus and any other immunosuppressant that the patient may currently be taking. This has become possible due to the development of highly sensitive and specific LC-MS/MS assays for the quantification of tacrolimus and other immunosuppressants in very small blood volumes such as dried blood spots (typically 20 µl of blood) 25,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] . Another advantage is that minimally invasive, low volume sample collection strategies such as dried blood spots greatly facilitate therapeutic drug monitoring and pharmacokinetic studies in small children 28 .…”

Section: Introductionmentioning

confidence: 99%

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Shokati

Bodenberger

Gadpaille

et al. 2015

JoVE

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The calcineurin inhibitor tacrolimus is the cornerstone of most immunosuppressive treatment protocols after solid organ transplantation in the United States. Tacrolimus is a narrow therapeutic index drug and as such requires therapeutic drug monitoring and dose adjustment based on its whole blood trough concentrations. To facilitate home therapeutic drug and adherence monitoring, the collection of dried blood spots is an attractive concept. After a finger stick, the patient collects a blood drop on filter paper at home. After the blood is dried, it is mailed to the analytical laboratory where tacrolimus is quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in combination with a simple manual protein precipitation step and online column extraction.For tacrolimus analysis, a 6-mm disc is punched from the saturated center of the blood spot. The blood spot is homogenized using a bullet blender and then proteins are precipitated with methanol/0.2 M ZnSO 4 containing the internal standard D 2, 13 C-tacrolimus. After vortexing and centrifugation, 100 µl of supernatant is injected into an online extraction column and washed with 5 ml/min of 0.1 formic acid/acetonitrile (7:3, v:v) for 1 min. Hereafter, the switching valve is activated and the analytes are back-flushed onto the analytical column (and separated using a 0.1% formic acid/acetonitrile gradient). Tacrolimus is quantified in the positive multi reaction mode (MRM) using a tandem mass spectrometer.The assay is linear from 1 to 50 ng/ml. Inter-assay variability (3.6%-6.1%) and accuracy (91.7%-101.6%) as assessed over 20 days meet acceptance criteria. Average extraction recovery is 95.5%. There are no relevant carry-over, matrix interferences and matrix effects. Tacrolimus is stable in dried blood spots at RT and at +4 °C for 1 week. Extracted samples in the autosampler are stable at +4 °C for at least 72 hr. Video LinkThe video component of this article can be found at

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“…The potential applications of this technology are broad and include field studies in resource-limited settings and the use of patient-self collected specimens that could facilitate monitoring for patients who do not have convenient access to phlebotomy facilities or who are unwilling to undergo venipuncture. This could be particularly relevant for transplant patients, since DBS have also been shown to be suitable for assessing levels of immunosuppressant medications (20). Thus, theoretically, two of the most commonly monitored analytes in transplant patients (immunosuppressant-drug levels and viral load) could potentially be assessed in patient selfcollected DBS samples that are sent to central laboratory facilities using the standard United States mail system.…”

Section: Discussionmentioning

confidence: 99%

Quantitation of Cytomegalovirus DNA Load in Dried Blood Spots Correlates Well with Plasma Viral Load

et al. 2013

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An assay to accurately quantitate cytomegalovirus (CMV) load in finger-stick-collected dried blood spots (DBS) could potentially be useful for field studies or for analyzing patient self-collected specimens. We therefore assessed CMV DNA load in paired venipuncture-collected plasma samples and finger-stick DBS, using a previously validated quantitative PCR assay. Assay variability, sensitivity, and changes in viral load during antiviral therapy in finger-stick DBS were compared to the reference plasma quantitative PCR assay, using 106 prospectively collected pairs of finger-stick DBS and plasma samples from 35 solid-organ transplant (SOT) patients. The DBS assay showed good agreement with the reference plasma viral load assay on the log 10 scale (Pearson correlation coefficient, 0.92; P < 0.001). The 95% limit of detection of the DBS assay was estimated at 2,700 plasma copies/ml (675 plasma IU/ml). In 94% (76/81) of paired DBS and plasma samples above the limit of detection, the difference in CMV load was <1 log 10 . CMV viral load changes during antiviral treatment were comparable in plasma and DBS. We conclude that finger-stick DBS provides a convenient sample type for quantitation of CMV load that correlates well with plasma levels. Future studies to optimize and evaluate this methodology for patient self-collected samples are warranted.A ssessment of cytomegalovirus (CMV) load in blood has been shown to be clinically useful in various patient populations (1). In transplant recipients, quantitation of CMV load in blood (plasma, whole blood, peripheral blood mononuclear cells, or lymphocytes) is commonly used for diagnosis of CMV disease, as a marker for initiating antiviral therapy in patients receiving preemptive therapy, and for monitoring response to therapy (1). Typically, CMV quantitation is performed using blood collected by phlebotomy (venipuncture). However, this approach requires that patients have access to facilities and personnel where phlebotomy can be performed. This can be a limitation in situations where such access is not readily available (field studies in resourcelimited settings or for patients who live long distances from medical facilities).Several previous studies described the use of dried blood spots (DBS) for detection of CMV (2-12). However, most of these prior studies using DBS for detection of CMV focused on children with congenital CMV infection, where quantitation and monitoring of viral load over time are not routinely performed. Other limitations of prior studies have included relatively small numbers of patients, use of systematically spotted cards with known pipetted venipuncture-collected blood volumes (rather than utilizing actual finger-stick blood, in which precise volumes are not known and homogeneity of blood on cards is not ensured), lack of comparison with concomitantly collected blood samples, or lack of serially collected specimens for assessment of viral load changes during treatment. To our knowledge, there are no prior published studies that have specifically fo...

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Dried Blood Spot Measurement of Tacrolimus Is Promising for Patient Monitoring

Cited by 58 publications

References 6 publications

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Quantitation of Cytomegalovirus DNA Load in Dried Blood Spots Correlates Well with Plasma Viral Load

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