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Volumetric absorptive microsampling as an alternative tool for therapeutic drug monitoring of first-generation anti-epileptic drugs.
Anal Bioanal Chem 2018; 410(9):2331-2341AB

Abstract

Dosage adjustment of anti-epileptic drugs by therapeutic drug monitoring (TDM) is very useful, especially for the first-generation anti-epileptic drugs (AEDs). Microsampling-the collection of small volumes of blood-is increasingly considered a valuable alternative to conventional venous sampling for TDM. Volumetric absorptive microsampling (VAMS) allows accurate and precise collection of a fixed volume of blood, eliminating the volumetric blood hematocrit bias coupled to conventional dried blood spot collection. The aim of this study was to develop and validate an LC-MS/MS method for the determination and quantification of four anti-epileptic drugs (carbamazepine, valproic acid, phenobarbital, and phenytoin) and one active metabolite (carbamazepine-10,11-epoxide) in samples collected by VAMS. The method was fully validated based on international guidelines. Precision (%RSD) was below 10%, while, with a single exception, accuracy (%bias) met the acceptance criteria. Neither carry-over nor unacceptable interferences were observed, the method being able to distinguish between the isomers oxcarbazepine and carbamazepine-10,11-epoxide. All compounds were stable in VAMS samples for at least 1 month when stored at room temperature, 4 °C, and - 20 °C and for at least 1 week when stored at 60 °C. Internal standard-corrected matrix effects were below 10%, with %RSDs below 4%. High (> 85%) recovery values were obtained and the effect of the hematocrit on the recovery was overall limited. Successful application on external quality control materials and on left-over patient samples demonstrated the validity and applicability of the developed procedure. Graphical abstract Graphical representation of the sampling, chemical structures, and the resulting chromatogram for volumetric absorptive microsampling (VAMS)-based therapeutic drug monitoring of first-generation anti-epileptic drugs by liquid chromatography with tandem mass spectrometric detection.

Authors+Show Affiliations

Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. christophe.stove@ugent.be.

Pub Type(s)

Journal Article
Validation Studies

Language

eng

PubMed ID

29362853

Citation

Velghe, Sofie, and Christophe P. Stove. "Volumetric Absorptive Microsampling as an Alternative Tool for Therapeutic Drug Monitoring of First-generation Anti-epileptic Drugs." Analytical and Bioanalytical Chemistry, vol. 410, no. 9, 2018, pp. 2331-2341.
Velghe S, Stove CP. Volumetric absorptive microsampling as an alternative tool for therapeutic drug monitoring of first-generation anti-epileptic drugs. Anal Bioanal Chem. 2018;410(9):2331-2341.
Velghe, S., & Stove, C. P. (2018). Volumetric absorptive microsampling as an alternative tool for therapeutic drug monitoring of first-generation anti-epileptic drugs. Analytical and Bioanalytical Chemistry, 410(9), pp. 2331-2341. doi:10.1007/s00216-018-0866-4.
Velghe S, Stove CP. Volumetric Absorptive Microsampling as an Alternative Tool for Therapeutic Drug Monitoring of First-generation Anti-epileptic Drugs. Anal Bioanal Chem. 2018;410(9):2331-2341. PubMed PMID: 29362853.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Volumetric absorptive microsampling as an alternative tool for therapeutic drug monitoring of first-generation anti-epileptic drugs. AU - Velghe,Sofie, AU - Stove,Christophe P, Y1 - 2018/01/23/ PY - 2017/11/20/received PY - 2018/01/08/accepted PY - 2017/12/24/revised PY - 2018/1/25/pubmed PY - 2018/5/2/medline PY - 2018/1/25/entrez KW - Alternative sampling strategies KW - Anti-epileptic drugs KW - Liquid chromatography-tandem mass spectrometry KW - Sample preparation KW - Volumetric absorptive microsampling SP - 2331 EP - 2341 JF - Analytical and bioanalytical chemistry JO - Anal Bioanal Chem VL - 410 IS - 9 N2 - Dosage adjustment of anti-epileptic drugs by therapeutic drug monitoring (TDM) is very useful, especially for the first-generation anti-epileptic drugs (AEDs). Microsampling-the collection of small volumes of blood-is increasingly considered a valuable alternative to conventional venous sampling for TDM. Volumetric absorptive microsampling (VAMS) allows accurate and precise collection of a fixed volume of blood, eliminating the volumetric blood hematocrit bias coupled to conventional dried blood spot collection. The aim of this study was to develop and validate an LC-MS/MS method for the determination and quantification of four anti-epileptic drugs (carbamazepine, valproic acid, phenobarbital, and phenytoin) and one active metabolite (carbamazepine-10,11-epoxide) in samples collected by VAMS. The method was fully validated based on international guidelines. Precision (%RSD) was below 10%, while, with a single exception, accuracy (%bias) met the acceptance criteria. Neither carry-over nor unacceptable interferences were observed, the method being able to distinguish between the isomers oxcarbazepine and carbamazepine-10,11-epoxide. All compounds were stable in VAMS samples for at least 1 month when stored at room temperature, 4 °C, and - 20 °C and for at least 1 week when stored at 60 °C. Internal standard-corrected matrix effects were below 10%, with %RSDs below 4%. High (> 85%) recovery values were obtained and the effect of the hematocrit on the recovery was overall limited. Successful application on external quality control materials and on left-over patient samples demonstrated the validity and applicability of the developed procedure. Graphical abstract Graphical representation of the sampling, chemical structures, and the resulting chromatogram for volumetric absorptive microsampling (VAMS)-based therapeutic drug monitoring of first-generation anti-epileptic drugs by liquid chromatography with tandem mass spectrometric detection. SN - 1618-2650 UR - https://www.unboundmedicine.com/medline/citation/29362853/Volumetric_absorptive_microsampling_as_an_alternative_tool_for_therapeutic_drug_monitoring_of_first_generation_anti_epileptic_drugs_ L2 - https://dx.doi.org/10.1007/s00216-018-0866-4 DB - PRIME DP - Unbound Medicine ER -