Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications

Déglon, Julien; Thomas, Aurélien; Mangin, Patrice; Staub, Christian

doi:10.1007/s00216-011-5161-6

Cited by 127 publications

(92 citation statements)

References 72 publications

(85 reference statements)

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“…Although for these particular analyses we use "on-spot derivatization" and GC-MS [67][68][69] , the use of dried (blood, urine, …) spots as an analytical tool (also allowing automation -see section 5.1) prior to LC-MS/MS can be applied for other compounds as well 6,70,71 . When considering toxicology screening in an acute setting, liquid microsampling, coupled to e.g.…”

Section: Toxicologymentioning

confidence: 99%

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

Velghe

Capiau

Stove

2016

TrAC Trends in Analytical Chemistry

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Alternative sampling strategies such as dried blood sampling, liquid microsampling and the sampling of oral fluid, hair, meconium, interstitial fluid, sweat, exhaled breath condensate and sputum offer interesting opportunities for many applications in clinical routine. Here, we provide an overview of different applications, with special attention to the pivotal role of LC-MS/MS in facilitating analysis of the collected matrices. Covered clinical fields include newborn screening, endocrinology, therapeutic drug monitoring, phenotyping, toxicology, proteomics and metabolomics. Furthermore, specific advantages, challenges and limitations of each alternative sampling strategy are discussed, along with recent advances and future trends that may contribute to routine implementation of these sampling strategies. Given the development of many recent potentially valuable clinical applications, the possibility of home sampling and the opportunity to obtain information that is hard to procure using traditional sampling, a well-balanced role for alternative sampling strategies can be envisaged in patient healthcare in the (near) future.

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Section: Toxicologymentioning

confidence: 99%

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

Velghe

Capiau

Stove

2016

TrAC Trends in Analytical Chemistry

View full text Add to dashboard Cite

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“…This method has many disadvantages such as requires a large volume, inefficient in storage and distribution, need experts to obtain the blood, and painful to the patients [3,4]. Dried blood spot (DBS) sampling has many potential advantages such as minimum invasive because using a sterile lancet needle in the fingers, toes or heel, small sample volumes ranging from 10 to 80 µl, efficient storage and distribution, prolonged sample stability, lower risk of infections, and comfortable for the subject [5,6]. Because the sample is taken from a peripheral vein in small volume, causing the analyte and the hematocrit interfering with the quantitative analysis of the drug molecule.…”

Section: Introductionmentioning

confidence: 99%

Analysis of 6-Mercaptopurine and 6-Methylmercaptopurine in Dried Blood Spots Using Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Childhood Acute Lymphoblastic Leukemia Patients

Supandi

Harahap

Harmita

et al. 2017

Asian J Pharm Clin Res

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Objective: To analyze and validate 6-mercaptopurine (6-MP) and 6-methylmercaptopurine (6-MMP) in dried blood spots (DBS) using liquid chromatography-tandem mass spectrometry (LC/MS-MS).Methods: Bio-sampling dried blood spot with DBS-CAMAG ® paper diameter of 8 mm and extracted with acetonitrile-methanol (1:3) containing internal standard 5-fluorouracil (5-FU). Separation was performed with C 18 column Acquity ® 1.7 μm (2.1 mm × 100 mm), with a mobile phase mixture of 0.1% formic acid in water 0.1% formic acid in acetonitrile with gradient elution and flow rate 0.2 ml/min. Mass detection was Waters Xevo TQD with positive electrospray ionization (ESI) for 6-MP, 6-MMP and negative ESI for 5-FU in multiple reaction monitoring modes. The ions of 6-MP was detected at m/z 153.09->119.09, 6-MMP at m/z 167.17->126.03, and 5-FU at m/z 129.15->42.05. Results:This method fulfill the requirements of selectivity, linearity, lower limit of quantification, accuracy, precision, carry-over, matrix effects, and stability which refers to the european medicines agency (EMEA) guidelines. The linearity of 0.99 was 26-1000 ng/mL for 6-MP and 6-MMP, respectively. The validated method was applied to two childhood ALL maintenance phase. Retrieved 6-MP levels of 10.37 pmol/8×10 8 erythrocytes, respectively. The levels of 6-MMP gained 16.59 pmol/8×10 8 erythrocytes, respectively. Conclusion:The developed LC/MS-MS method is valid to analysis 6-MP and 6-MMP in DBS simultaneous in vitro according to EMEA guidelines. The method was successfully applied to authentic capillary blood samples from two childhood patients with ALL in the maintenance phase.

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“…Another advantage is the small amount of blood is taken (10-80 µL). DBS is also convenient in respect of storage and distribution, while analysis of a sample of dried blood is relatively stable and this procedure reduces the risk of infection for the subject [6][7][8]. An analytical method for 6-MP and 6-MMP in plasma as well as in whole blood has already been developed; it uses high-performance liquid chromatography (HPLC) with the ultraviolet detector and ultra-PLC tandem mass spectrometry (UPLC-MS/MS) [5,9].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Analytical Method Development of 6-Mercaptopurine and 6-Methylmercaptopurine in Dried Blood Spot Using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry

et al. 2017

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Objective: 6-mercaptopurine (6-MP) is a chemotherapeutic agent in the antimetabolite class. It has to go through the metabolic pathway to form 6-methyl MP (6-MMP). This study aimed to obtain an optimum and validated method for the analysis of 6-MP and 6-MMP in dried blood spot (DBS) samples simultaneously and to evaluate the potential for future drug concentration monitoring in DBS samples. Methods:The quality control and calibration curves were made by spotting 40 µL blood on DBS paper and dried for 3 hrs. DBS papers were cut with a diameter of 8 mm and extracted with acetonitrile-methanol (1:3) containing internal standard 5-fluorouracil (5-FU). Separation was performed with waters acquity ultra performance liquid chromatography BEH C18 column of 1.7 μm (2.1×100 mm) with a mobile phase consisting of 0.1% formic acid in water 0.1% formic acid in acetonitrile with gradient elution and a flow rate of 0.2 mL/minute. Mass detection was performed using Waters Xevo TQD with positive electrospray ionization (ESI) for 6-MP and 6-MMP and negative ESI for 5-FU in the multiple reaction monitoring mode. Results:The detection rates of 6-MP, 6-MMP, and 5-FU were 153.09>119.09, 167.17>126.03, and 129.09>42.05, respectively. This method was linear with the range at 26-1000 ng/mL for 6-MP and 13-500 ng/mL for 6-MMP with consecutive r≥0.998 and ≥0.999, respectively. The % relative error value and % relative standard deviation for accuracy and precision of intraday and interday were not more than 15% and not more than 20% at the lower limit of quantification concentration, respectively. Conclusions:This method fulfilled the requirements of selectivity, linearity, carry over, and matrix effects referring to the European Medicines Agency guidelines.

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Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications

Cited by 127 publications

References 72 publications

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

Analysis of 6-Mercaptopurine and 6-Methylmercaptopurine in Dried Blood Spots Using Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Childhood Acute Lymphoblastic Leukemia Patients

Simultaneous Analytical Method Development of 6-Mercaptopurine and 6-Methylmercaptopurine in Dried Blood Spot Using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry

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