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Volumetric Absorptive Microsampling: A New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs.
Ther Drug Monit 2019; 41(5):681-692TD

Abstract

BACKGROUND

Volumetric absorptive microsampling (VAMS) is a novel sampling technique for the collection of fixed-volume capillary blood. In this study, a new analytical method was developed and used to quantify 14 different antiepileptic drugs (AEDs) and 2 active metabolites in samples collected by VAMS. These data were compared with concentration measurements in plasma.

METHODS

The authors developed a selective and sensitive liquid chromatography-mass spectrometry (LC-MS/MS) assay to measure the concentrations of several AEDs in whole blood collected by VAMS, which were compared with a commercially available LC-MS/MS kit for AED monitoring in plasma. Drugs and internal standards were extracted from whole blood/plasma samples by a simple protein precipitation.

RESULTS

An LC-MS/MS method analyzing VAMS samples was successfully developed and validated for the determination of various AED concentrations in whole blood according to EMA guidelines for bioanalytical method validation. Extraction recovery was between 91% and 110%. No matrix effect was found. The method was linear for all drugs with R ≥0.989 in all cases. Intra-assay and inter-assay reproducibility analyses demonstrated accuracy and precision within acceptance criteria. Carry over and interferences were negligible. No volumetric HCT% bias was found at 3 different HCT values (35%-55%) with recovery being consistently above 87%. Samples are very stable at temperatures ranging from -20°C to 37°C and for a 4-month period. Leftover EDTA samples from 133 patients were tested to determine concentration differences between plasma and whole blood sampled by VAMS. The resulting difference varied less than 15% apart from those drugs with a blood/plasma ratio (R) different from 1.

CONCLUSIONS

The assay allows for highly sensitive and selective quantification of several AEDs in whole blood samples collected by VAMS. The developed method is accurate and precise and free from matrix effects and volumetric HCT% bias.

Authors+Show Affiliations

Laboratory of Neurological Biochemistry and Neuropharmacology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.Neoteryx LLC, Torrance, California.UCL Queen Square Institute of Neurology, London. Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom.Laboratory of Neurological Biochemistry and Neuropharmacology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31095069

Citation

DʼUrso, Annachiara, et al. "Volumetric Absorptive Microsampling: a New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs." Therapeutic Drug Monitoring, vol. 41, no. 5, 2019, pp. 681-692.
DʼUrso A, Rudge J, Patsalos PN, et al. Volumetric Absorptive Microsampling: A New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs. Ther Drug Monit. 2019;41(5):681-692.
DʼUrso, A., Rudge, J., Patsalos, P. N., & de Grazia, U. (2019). Volumetric Absorptive Microsampling: A New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs. Therapeutic Drug Monitoring, 41(5), pp. 681-692. doi:10.1097/FTD.0000000000000652.
DʼUrso A, et al. Volumetric Absorptive Microsampling: a New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs. Ther Drug Monit. 2019;41(5):681-692. PubMed PMID: 31095069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Volumetric Absorptive Microsampling: A New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs. AU - DʼUrso,Annachiara, AU - Rudge,James, AU - Patsalos,Philip N, AU - de Grazia,Ugo, PY - 2019/5/17/pubmed PY - 2019/5/17/medline PY - 2019/5/17/entrez SP - 681 EP - 692 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 41 IS - 5 N2 - BACKGROUND: Volumetric absorptive microsampling (VAMS) is a novel sampling technique for the collection of fixed-volume capillary blood. In this study, a new analytical method was developed and used to quantify 14 different antiepileptic drugs (AEDs) and 2 active metabolites in samples collected by VAMS. These data were compared with concentration measurements in plasma. METHODS: The authors developed a selective and sensitive liquid chromatography-mass spectrometry (LC-MS/MS) assay to measure the concentrations of several AEDs in whole blood collected by VAMS, which were compared with a commercially available LC-MS/MS kit for AED monitoring in plasma. Drugs and internal standards were extracted from whole blood/plasma samples by a simple protein precipitation. RESULTS: An LC-MS/MS method analyzing VAMS samples was successfully developed and validated for the determination of various AED concentrations in whole blood according to EMA guidelines for bioanalytical method validation. Extraction recovery was between 91% and 110%. No matrix effect was found. The method was linear for all drugs with R ≥0.989 in all cases. Intra-assay and inter-assay reproducibility analyses demonstrated accuracy and precision within acceptance criteria. Carry over and interferences were negligible. No volumetric HCT% bias was found at 3 different HCT values (35%-55%) with recovery being consistently above 87%. Samples are very stable at temperatures ranging from -20°C to 37°C and for a 4-month period. Leftover EDTA samples from 133 patients were tested to determine concentration differences between plasma and whole blood sampled by VAMS. The resulting difference varied less than 15% apart from those drugs with a blood/plasma ratio (R) different from 1. CONCLUSIONS: The assay allows for highly sensitive and selective quantification of several AEDs in whole blood samples collected by VAMS. The developed method is accurate and precise and free from matrix effects and volumetric HCT% bias. SN - 1536-3694 UR - https://www.unboundmedicine.com/medline/citation/31095069/Volumetric_Absorptive_Microsampling:_A_New_Sampling_Tool_for_Therapeutic_Drug_Monitoring_of_Antiepileptic_Drugs_ L2 - http://dx.doi.org/10.1097/FTD.0000000000000652 DB - PRIME DP - Unbound Medicine ER -