Therapeutic drug monitoring of Antiepileptic drugs in

Therapeutic Drug Monitoring Of Antiepileptic Drugs In-Free PDF

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Therapeutic drug monitoring of Antiepileptic drugs in serum. a fully automated approach,Introduction, Epilepsy is a chronic neurological disorder which is N Desmethylmethsuximide NDMS Oxcarbazepine. characterized by recurrent epileptic seizures whose Phenylethylmalonamide PEMA Perampanel Phenobarbital. frequency and rhythm are mostly not predictable For the Phenytoin Pregabaline Primidone Retigabine Rufinamide. pharmacological therapy of epilepsy a variety of Stiripentol Sulthiame Tiagabine Topiramate Valproic. antiepileptic drugs AEDs are available today most of acid Zonisamide in serum samples by LC MS MS analysis. them exhibit a pronounced intra and inter individual Usually LC MS MS analysis of serum samples require. variability in pharmacokinetics For that reason the manual preparation steps for extraction and protein. therapeutic drug monitoring of these molecules needs to precipitation before the injection With the aim to reduce. be accomplished by extremely accurate techniques e g the operator involvement and to increase the throughput. LC MS MS LC MS MS currently lacks in standardization and data quality we completely eliminated the. and throughput for routine analysis We report a method involvement of the operator for sample preparation by the. for the quantitation of 26 AEDs 10 OH Carbamazepine use of a novel automatic preparation unit CLAM 2000. Carbamazepine Carbamazepine Diol Carbamazepine Shimadzu the present work is intended for research use. Epoxide Ethosuximide Felbamate Gabapentin only,Lacosamide Lamotrigine Levetiracetam. Carbamazepine Ethosuximide Felbamate,Lacosamide Stiripentol. Pregabalin Rufinamide Lamotrigine, Figure 1 Structure of the most common antiepileptic drugs. Therapeutic drug monitoring of Antiepileptic drugs in serum. a fully automated approach,Methods and Materials, The analysis of Antiepileptic drugs was performed using MS9200 Samples calibrators Recipe ClinCal.
a fully automatic LCMS preparation Unit CLAM 2000 MS9213 and Internal standard mix Recipe ClinMass. For Research Use Only Not for use in clinical MS9212 were loaded onto the CLAM 2000. diagnostics Shimadzu online with a LCMS system refrigerated at 8 C Figure 2 The quantitation of AEDs. NexeraX2 LCMS8060 Shimadzu starting from serum in serum samples was performed by LC MS MS analysis. samples using the ClinMass TDM Kit System Recipe Table 1. Table 1 MRM Transitions for all the analytes, SIM analisys 140 00 140 00 was added as additional reference Ion. Molecule Quantifier Qualifier,Gabapentine 171 70 137 10 171 80 55 10. Levitiracetam 170 70 126 00 170 70 69 00,Pregabalin 160 00 142 00 160 00 97 20. PEMA 207 00 91 10 207 00 117 10,D5 PEMA 211 80 93 10 211 80 167 15. Lacosamid 250 80 91 00 250 80 71 10,D3 Lacosamid 253 90 91 15 253 90 108 15.
Primidon 219 00 162 10 219 00 91 00,CBZ Diol 271 00 180 00 271 00 210 00. Felbamat 239 00 117 30 239 20 64 70,Lamotrigin 255 90 43 00 255 90 58 20. 10 OH CBZ 254 60 194 00 254 60 165 00,Rufinamid 238 70 127 15 238 70 100 95. CBZ Epoxid 252 70 180 00 252 70 236 10,Oxacarbazepin 252 70 180 00 252 70 236 10. CBZ 236 80 165 00 236 80 194 00,Phenytoin 253 10 181 90 253 00 104 10.
Tiagabin 376 20 246 90 375 90 149 20,Perampanel 349 70 247 00 349 70 219 00. Retigabin 303 80 109 00 303 80 230 00,D6 Tiagabin 382 10 253 00 382 10 114 00. D4 Retigabin 307 70 112 95 307 70 234 05,Stiripentol 217 00 187 10 217 00 159 00. Ethosuximid 140 00 42 00 140 00 11 0,Sultiam 288 70 225 30 288 70 132 20. Valpronic acid 143 00 143 00,Zonisamid 210 80 119 10 210 80 63 90.
Phenobarbital 230 90 41 90 230 90 41 90,NDMS 187 90 42 00 187 90 42 00. Topriamat 337 70 78 00 337 80 95 90, Therapeutic drug monitoring of Antiepileptic drugs in serum. a fully automated approach, Figure 2 CLAM 2000 online with Nexera X2 system and. LCMS 8060 triple quadrupole mass spectrometer,Fully Automated sample preparation. The CLAM 2000 was programmed to perform sample extraction and protein precipitation followed by filtration and. sample collection The filtrated sample was then automatically transported using an arm from the CLAM 2000 to the. HPLC for LC MS MS analysis and no human intervention was required Figure 3. Figure 3 CLAM 2000 fully automated sample preparation and analysis. Due to the overlapped sample preparation the throughput of the instrument was. 1 result each 6 minutes for quantification of all Atiepileptics. Therapeutic drug monitoring of Antiepileptic drugs in serum. a fully automated approach,Methods correlation, Fully automated sample preparation method was finally compared with manual sample preparation method by.
analyzing several serum samples spiked with all the analytes at various concentration levels The method correlation. was evaluated through Passing Bablok plot Figure 4. Figure 4 Methods comparison using Passing Bablok plot. 20 serum samples spiked at different concentrations of all AEDs. Linearity Accuracy and Precision, The linearity and accuracy of the method was evaluated using 3 reference serum calibrators levels Recipe MS9213. For all the analytes linearity and accuracy were within the analytical acceptable range 85 115 Furthermore in. order to estimate the precision of the method reference serum samples Recipe MS9282 spanning from low. concentration level to high concentration level were analyzed several times 6 replicates For all analytes the CV. values were within acceptable analytical ranges, Therapeutic drug monitoring of Antiepileptic drugs in serum. a fully automated approach, Table 4 Linearity Accuracy and precision evaluated using ClinChek MS9282 reference serum controls. n 6 replicates n 3 non consecutive days,PRECISION CV. ACCURACY BIAS,Compound R2,INTRADAY INTERDAY,Min Max Low High Low High Low High.
Gabapentin 0 999 100 100 5 6 3 3 7 1 4 7 2 9 9 5, Levitiracetam 0 999 95 9 106 4 2 4 2 3 9 3 9 12 7 14 8. Pregabalin 0 998 94 4 108 3 1 2 2 3 4 2 3 3 3 6 1,PEMA 0 998 94 4 108 1 6 1 2 2 4 1 9 3 1 2 8. Lacosamide 0 999 96 5 105 1 3 3 0 3 6 2 1 5 2 3 1,Primidone 0 999 96 0 106 5 4 4 2 6 8 4 3 8 4 5 1. CBZ Diol 0 998 95 5 106 4 5 4 2 4 9 4 8 0 5 4 1,Felbamate 0 999 98 1 103 1 5 1 2 4 3 4 5 1 8 2 6. Lamotrigine 0 940 80 123 2 9 2 8 10 4 3 2 6 2 0 3,10 OH CBZ 0 994 92 9 106 6 2 1 2 5 3 6 2 3 5 9 2.
Rufinamide 0 996 95 106 4 2 2 6 3 6 2 5 3 4 3 9, CBZ Epoxide 0 999 96 2 103 1 5 2 8 2 6 2 4 n d n d. Oxacarbazepine 0 997 95 5 105 2 2 1 3 3 3 1 7 1 7 6 5. CBZ 0 999 98 8 100 4 0 3 9 4 5 4 5 9 4 1 8,Phenytoin 0 999 94 5 102 6 2 2 2 6 1 5 2 2 8 9 4. Tiagabine 0 999 96 2 101 5 1 5 5 6 0 4 5 3 1 1 4, Perampanel 0 999 97 3 104 6 1 4 6 8 9 4 1 12 7 15 4. Retigabine 0 97 85 9 116 6 8 5 6 8 8 5 3 11 0 0 8, Stiripentol 0 999 96 7 105 4 9 2 2 4 6 3 4 5 2 2 6. Ethosuximide 0 999 96 1 101 7 3 9 6 10 8 11 2 4 3 1 1. Sultiame 0 999 97 3 104 4 2 4 4 4 5 5 5 9 3 8 4, Valpronic acid 0 999 97 7 103 8 8 3 4 6 6 3 9 6 0 2 1.
Zonisamide 0 999 97 2 101 3 7 3 4 3 9 2 9 11 6 5 2. Phenobarbital 0 996 94 3 105 6 5 5 1 6 1 4 6 1 5 2 5. NDMS 0 999 97 5 103 11 3 5 3 8 9 5 5 1 0 7 1, Topiramate 0 998 96 2 105 8 2 6 3 13 0 6 3 3 1 3 2. Therapeutic drug monitoring of Antiepileptic drugs in serum. a fully automated approach,Conclusions, Fully Automated sample preparation procedure resulted suitable for the quantitation of Antiepileptic drugs by. elimination of all manual preparation steps, The automation of the method increases the analytical performance reduces the risk for human operators and due to. the reduced reagent consumption reduces also the cost of the analysis. Disclaimer The products and applications in this presentation are intended for Research Use Only RUO Not for. use in diagnostic procedures Not available in the USA Canada and China. First Edition June 2017,Shimadzu Corporation 2017,. antiepileptic drugs AEDs are available today most of them exhibit a pronounced intra and inter individual variability in pharmacokinetics For that reason the therapeutic drug monitoring of these molecules needs to be accomplished by extremely accurate techniques e g LC MS MS LC MS MS currently lacks in standardization and throughput for routine analysis We report a method for the

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