TY - JOUR
T1 - High-speed simultaneous determination of nine antiepileptic drugs using liquid chromatography-mass spectrometry
AU - Subramanian, Murali
AU - Birnbaum, Angela K.
AU - Remmel, Rory P.
PY - 2008/6
Y1 - 2008/6
N2 - Therapeutic drug monitoring of antiepileptic drugs (AEDs) is important and widely practiced. However, simultaneous AED assays usually concentrate only on old or new AEDs. A new simultaneous assay was developed to monitor both older and newer AEDs in the same sample. This assay measures zonisamide (ZNS), lamotrigine (LTG), topiramate (TPM), phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), carbamazepine-10,11-diol (CBZ-Diol), 10- hydroxycarbamazepine (MHD), and carbamazepine-10,11-epoxide (CBZ-E). Sample pretreatment consisted of a single solid-phase extraction (SPE) for all AEDs in a 100-μL plasma sample. HPLC separation was achieved on a Shimdazu Shimpack XR-ODS (4.6 id × 50 mm, 2.2-μm) column with a gradient mobile phase of acetate buffer, methanol, acetonitrile, and tetrahydrofuran. Four internal standards were used. Detection was achieved by atmospheric pressure chemical ionization mass spectrometry (APCI-MS) in selected-ion monitoring (SIM) mode with constant polarity switching. High recovery (88%-96%) was obtained for all compounds by SPE. Linearity was observed throughout an 80-fold concentration range, with correlation coefficient (r 2) values higher than 0.99 for all AEDs. For the standards, the accuracy ranged from 89.3% to 111.8%. The within-run coefficient of variation (CV w) value was ≤9.7%, the between-run coefficient of variation (CV b) was ≤16.2%, and the total variability (CV t) was ≤16.8%. For the quality controls (QCs), accuracy ranged from 89.3% to 108.8%, CV w was ≤9.6%, CV b was ≤14.1%, and CV t was ≤15.1%. The correlation r 2 values for comparison of this assay with existing validated assays in our laboratory (GC-MS or LC-MS) were 0.95, 0.91, 0.87, 0.95, and 0.95 for PHT, LTG, CBZ, CBZ-E, and CBZ-Diol, respectively.
AB - Therapeutic drug monitoring of antiepileptic drugs (AEDs) is important and widely practiced. However, simultaneous AED assays usually concentrate only on old or new AEDs. A new simultaneous assay was developed to monitor both older and newer AEDs in the same sample. This assay measures zonisamide (ZNS), lamotrigine (LTG), topiramate (TPM), phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), carbamazepine-10,11-diol (CBZ-Diol), 10- hydroxycarbamazepine (MHD), and carbamazepine-10,11-epoxide (CBZ-E). Sample pretreatment consisted of a single solid-phase extraction (SPE) for all AEDs in a 100-μL plasma sample. HPLC separation was achieved on a Shimdazu Shimpack XR-ODS (4.6 id × 50 mm, 2.2-μm) column with a gradient mobile phase of acetate buffer, methanol, acetonitrile, and tetrahydrofuran. Four internal standards were used. Detection was achieved by atmospheric pressure chemical ionization mass spectrometry (APCI-MS) in selected-ion monitoring (SIM) mode with constant polarity switching. High recovery (88%-96%) was obtained for all compounds by SPE. Linearity was observed throughout an 80-fold concentration range, with correlation coefficient (r 2) values higher than 0.99 for all AEDs. For the standards, the accuracy ranged from 89.3% to 111.8%. The within-run coefficient of variation (CV w) value was ≤9.7%, the between-run coefficient of variation (CV b) was ≤16.2%, and the total variability (CV t) was ≤16.8%. For the quality controls (QCs), accuracy ranged from 89.3% to 108.8%, CV w was ≤9.6%, CV b was ≤14.1%, and CV t was ≤15.1%. The correlation r 2 values for comparison of this assay with existing validated assays in our laboratory (GC-MS or LC-MS) were 0.95, 0.91, 0.87, 0.95, and 0.95 for PHT, LTG, CBZ, CBZ-E, and CBZ-Diol, respectively.
KW - Antiepileptic drugs (AEDs)
KW - Carbamazepine
KW - LC-MS
KW - Lamotrigine
KW - Simultaneous assay
KW - Solid-phase extraction
KW - Zonisamide
UR - http://www.scopus.com/inward/record.url?scp=47249102459&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47249102459&partnerID=8YFLogxK
U2 - 10.1097/FTD.0b013e3181678ecb
DO - 10.1097/FTD.0b013e3181678ecb
M3 - Article
C2 - 18520607
AN - SCOPUS:47249102459
SN - 0163-4356
VL - 30
SP - 347
EP - 356
JO - Therapeutic drug monitoring
JF - Therapeutic drug monitoring
IS - 3
ER -