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Fully validated method for rapid and simultaneous measurement of six antiepileptic drugs in serum and plasma using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
Talanta. 2013 Jun 15; 110:71-80.T

Abstract

Therapeutic drug monitoring (TDM) may be very useful in the clinical management of antiepileptic drug therapy for multiple reasons, such as individual variability, metabolism, genetic factors or drug-drug or drug-food interactions. In addition, TDM is helpful to study the variation in pharmacokinetics that occurs between individuals. Here, we describe a rapid assay using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry to measure the antiepileptic drugs lacosamide, lamotrigine, levetiracetam, primidone, topiramate, and zonisamide. After the addition of internal standards (ISs) and protein precipitation of serum or plasma, 1 μl of sample was separated on a 2.1×50 mm reverse phase column (Waters, Acquity UPLC BEH Phenyl, 1.7 μm). Analytes were then ionized and detected by electrospray ionization mass spectrometry with multiple reaction monitoring. Runtime was 2.5 min per injection. Matrix effects were investigated by systematical ion suppression and in-source fragmentation experiments. The calibration curves of the 6 antiepileptic drugs were linear over the working range between 0.05 and 50 mg/L (r>0.99). The limit of detection (LOD) was <0.05 mg/L, whereas the limit of quantification (LLOQ) was 0.10 mg/L of all drugs measured in the assay. The intraassay and interassay coefficients of variation for all compounds were <15% for very low concentration (0.1 mg/L) and <8% in the clinically relevant concentration range (>1.0 mg/L). Mean recoveries were between 87.8 and 98.6% for all drugs. There were no significant ion suppressions detected at the elution times of the analytes. The mean differences between serum and heparinized plasma values were less than 6% for the 6 antiepileptic drugs. All drugs were stable in serum at -20°C, 4°C, and even at RT for at least 1 month. In summary, a specific and sensitive stable isotope dilution UPLC-MS/MS method was developed and validated for routine clinical monitoring of lacosamide, lamotrigine, levetiracetam, primidone, topiramate, and zonisamide.

Authors+Show Affiliations

Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany. jkuhn@hdz-nrw.deNo affiliation info available

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

23618178

Citation

Kuhn, Joachim, and Cornelius Knabbe. "Fully Validated Method for Rapid and Simultaneous Measurement of Six Antiepileptic Drugs in Serum and Plasma Using Ultra-performance Liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry." Talanta, vol. 110, 2013, pp. 71-80.
Kuhn J, Knabbe C. Fully validated method for rapid and simultaneous measurement of six antiepileptic drugs in serum and plasma using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Talanta. 2013;110:71-80.
Kuhn, J., & Knabbe, C. (2013). Fully validated method for rapid and simultaneous measurement of six antiepileptic drugs in serum and plasma using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Talanta, 110, 71-80. https://doi.org/10.1016/j.talanta.2013.02.010
Kuhn J, Knabbe C. Fully Validated Method for Rapid and Simultaneous Measurement of Six Antiepileptic Drugs in Serum and Plasma Using Ultra-performance Liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry. Talanta. 2013 Jun 15;110:71-80. PubMed PMID: 23618178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fully validated method for rapid and simultaneous measurement of six antiepileptic drugs in serum and plasma using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry. AU - Kuhn,Joachim, AU - Knabbe,Cornelius, Y1 - 2013/02/13/ PY - 2012/10/12/received PY - 2013/01/26/revised PY - 2013/02/05/accepted PY - 2013/4/27/entrez PY - 2013/4/27/pubmed PY - 2013/10/29/medline SP - 71 EP - 80 JF - Talanta JO - Talanta VL - 110 N2 - Therapeutic drug monitoring (TDM) may be very useful in the clinical management of antiepileptic drug therapy for multiple reasons, such as individual variability, metabolism, genetic factors or drug-drug or drug-food interactions. In addition, TDM is helpful to study the variation in pharmacokinetics that occurs between individuals. Here, we describe a rapid assay using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry to measure the antiepileptic drugs lacosamide, lamotrigine, levetiracetam, primidone, topiramate, and zonisamide. After the addition of internal standards (ISs) and protein precipitation of serum or plasma, 1 μl of sample was separated on a 2.1×50 mm reverse phase column (Waters, Acquity UPLC BEH Phenyl, 1.7 μm). Analytes were then ionized and detected by electrospray ionization mass spectrometry with multiple reaction monitoring. Runtime was 2.5 min per injection. Matrix effects were investigated by systematical ion suppression and in-source fragmentation experiments. The calibration curves of the 6 antiepileptic drugs were linear over the working range between 0.05 and 50 mg/L (r>0.99). The limit of detection (LOD) was <0.05 mg/L, whereas the limit of quantification (LLOQ) was 0.10 mg/L of all drugs measured in the assay. The intraassay and interassay coefficients of variation for all compounds were <15% for very low concentration (0.1 mg/L) and <8% in the clinically relevant concentration range (>1.0 mg/L). Mean recoveries were between 87.8 and 98.6% for all drugs. There were no significant ion suppressions detected at the elution times of the analytes. The mean differences between serum and heparinized plasma values were less than 6% for the 6 antiepileptic drugs. All drugs were stable in serum at -20°C, 4°C, and even at RT for at least 1 month. In summary, a specific and sensitive stable isotope dilution UPLC-MS/MS method was developed and validated for routine clinical monitoring of lacosamide, lamotrigine, levetiracetam, primidone, topiramate, and zonisamide. SN - 1873-3573 UR - https://www.unboundmedicine.com/medline/citation/23618178/Fully_validated_method_for_rapid_and_simultaneous_measurement_of_six_antiepileptic_drugs_in_serum_and_plasma_using_ultra_performance_liquid_chromatography_electrospray_ionization_tandem_mass_spectrometry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-9140(13)00083-0 DB - PRIME DP - Unbound Medicine ER -