We performed two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) in 2009. The number of participating laboratories were 110, which is similar with that of previous 3 years. Average response rates were 97.8% in both trials, similar to those of previous years. Two kinds of control materials were requested to be tested in each trial so that each institution could find the possible systematic errors. The average drug item responded was 6.2 per institution, which was decreased slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, carbamazepine, phenytoin, and theophylline which were peformed in more than 63.8% of participating laboratories, followed by phenobarbital, cyclosporine, tacrolimus, vancomycin, lithium, methotrexate, amikacin, gentamicin, acetaminophen, tobramycin, salicylate, free phenytoin, amitryptyline, ethosuximide, and primidone. The widely used TDM analyzers were Abbott AxSym (26.9%), followed by Abbott TDx/TDxFLx (24.8%), Roche Cobas Integra (15.1%), Siemens Diagnostics Viva-E (5.5%), Roche cobas c501 (5.1%), Siemens Diagnostics Dimension (3.4%), and many other analyzers. The inter-laboratory coefficients of variations showed similar tendency comparing with those of the previous years. The number of participating laboratories for drug of abuse (DOA) tests were 19, which was slightly increased compared to that of the previous year. Average DOA items were 3.8~4.2. We found the good performance of participating laboratories for DOA. In conclusion, the TDM and DOA external quality assessment of 2009 showed similar performance comparing with that of the recent 3 years.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring ; Ethosuximide ; Gentamicins ; Korea ; Lithium ; Methotrexate ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) were performed in 2008. The number of participating laboratories were 114, which is similar with that of the previous year. Average response rates were 97.8% in both trials slightly lower than that of the previous year. Two kinds of control materials were requested to be tested in each trial so that each laboratory could know the possible systematic error. The average drug item was 6.3 per laboratory, which was decreased slightly from 6.8 in recent 5 years, and the maximum was 18 items. The most common test items were valproic acid, digoxin, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 52.1% of participating laboratories, followed by cyclosporine, vancomycin, tacrolimus, lithium, methotrexate, amikacin, tobramycin, gentamycin, acetaminophen, salicylate, free phenytoin, primidone, and amitryptyline. The widely used TDM analyzers were Abbott TDx/TDxFLx (35.3%), followed by Abbott AxSym (26.5%) and Roche Cobas Integra (17.3%), Abbott IMx (3.3%), and Siemens Viva E (3.0%). The inter-laboratory coefficients of variations showed similar tendency comparing with those of the previous years. The number of participating laboratories for drug of abuse tests were 17, which is similar to that of the previous year. Average drug item were 3.7 for the 1st trial. We found the relatively good performance as we got the correct answers for all laboratories except 2 laboratories. In conclusion, the TDM external quality assessment of 2008 showed grossly similar pattern comparing with that of previous year.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring ; Gentamicins ; Korea ; Lithium ; Methotrexate ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) were performed in 2007. Number of participating laboratories were increased to 109, by 5.63% increase comparing with the previous year. Response rates reached 98.7% for both trials slightly lower than that of the previous year. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.3 per institution, which was decreased slightly from 6.8 in recent 5 years. The most common test items were valproic acid, digoxin, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 55% of the participating laboratories, followed by cyclosporine, vancomycin, lithium, tacrolimus, methotrexate, amikacin, gentamicin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The inter-laboratory coefficients of variations showed simliar tendency comparing with those of the previous years. We started the proficiency test for drug of abuse from 2007 and got the response from 13 and 17 laboratories in the 1st and 2nd trial, respectively. Average drug items were 3.4 for the 2nd trial. We found the relatively good performances as we got the correct answers from all laboratories except 4 for each one mistake. In conclusion, the TDM external quality assessment of 2007 showed grossly similar pattern comparing with those of previous year and drug of abuse proficiency testing showed a relatively good performance.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring ; Gentamicins ; Korea ; Lithium ; Methotrexate ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) were performed in 2007. Number of participating laboratories were increased to 109, by 5.63% increase comparing with the previous year. Response rates reached 98.7% for both trials slightly lower than that of the previous year. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.3 per institution, which was decreased slightly from 6.8 in recent 5 years. The most common test items were valproic acid, digoxin, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 55% of the participating laboratories, followed by cyclosporine, vancomycin, lithium, tacrolimus, methotrexate, amikacin, gentamicin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The inter-laboratory coefficients of variations showed simliar tendency comparing with those of the previous years. We started the proficiency test for drug of abuse from 2007 and got the response from 13 and 17 laboratories in the 1st and 2nd trial, respectively. Average drug items were 3.4 for the 2nd trial. We found the relatively good performances as we got the correct answers from all laboratories except 4 for each one mistake. In conclusion, the TDM external quality assessment of 2007 showed grossly similar pattern comparing with those of previous year and drug of abuse proficiency testing showed a relatively good performance.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring ; Gentamicins ; Korea ; Lithium ; Methotrexate ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

AIMTo develop a rapid and feasible method based on micellar electrokinetic capillary chromatography (MECC) for the simultaneous determination of antiepileptic drugs (AEDs)--phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), primidone (PRM) and clonazepam (CZP) in human plasma.

METHODSSeveral factors that impact the separation of AEDs with MECC were investigated, such as concentration of sodium dodecyl sulfate (SDS), buffer compositions, pH, organic modifier, internal diameter and temperature, and an optimized MECC running condition was obtained the running buffer consisted of 8 mmol x L(-1) phosphate, 3 mmol x L(-1) sodium tetraborate, and 50 mmol x L(-1) sodium dodecylsulfate (SDS) (pH 8.0), containing acetonitrile (ACN) (18%) as organic modifier. Detection at 210 nm, run at 25 kV at 30 degrees C in a untreated fused silica capillary (50/45.5 cm length, 50 microm ID).

RESULTSThe reproducibility of both migration time and relative peak area with MECC analysis were appropriate for the intra- and inter-assay coefficients. The evaluated drugs concentration intervals of PRM 1.0-40.0 microg x mL(-1), PB 1.0-60.0 microg x mL(-1), PHT 1.0-40.0 microg x mL(-1), CBZ 1.0-40.0 microg x mL(-1), CZP 0.2-8.0 microg x mL(-1) were linear with correlation coefficients higher than 0.999 1, and coefficients of the variation of the points of the calibration curve lower than 10%. The recoveries of AEDs varied from 80.0% to 100.0%, depending on the drug, with coefficients of the variation lower than 10.0%.

CONCLUSIONThe MECC technique is showed to be rapid, simple, efficient and low cost when applied to monitoring therapeutic drugs in patient treated with a combination of PHT and other AEDs such as hepatic enzyme-inducing agents.

Anticonvulsants ; blood ; Buffers ; Carbamazepine ; blood ; Chromatography, Micellar Electrokinetic Capillary ; methods ; Clonazepam ; blood ; Epilepsy ; blood ; Humans ; Hydrogen-Ion Concentration ; Phenobarbital ; blood ; Phenytoin ; blood ; Primidone ; blood ; Sensitivity and Specificity ; Sodium Dodecyl Sulfate

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2005. The number of participating laboratories were increased to 95, by 6.7% comparing with the previous year. Response rates were 100.0% for both trials just like the two previous years. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.7 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were digoxin, valproic acid, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 65% of participating laboratories, followed by cyclosporine, lithium, vancomycin, tacrolimus, methotrexate, amikacin, gentamycin, tobramycin, salicylate, primidone, acetaminophen, free phenytoin, amitryptyline, and ethosuximide. The most widely used TDM analyzer was Abbott TDx/TDxFLx (41.7%), followed by Abbott AxSym (23.3%), and Roche Cobas Integra (19.2%). The inter-laboratory coefficients of variations were not much improved comparing with previous years. We also determined cyclosporine with reference method using liquid chromatography-tandem mass spectrometry. In conclusion, the TDM external quality assessment of 2005 showed grossly similar pattern comparing with those of previous year with increasing participating laboratories.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring* ; Ethosuximide ; Gentamicins ; Korea* ; Lithium ; Mass Spectrometry ; Methotrexate ; Pathology, Clinical ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) Subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2004. Number of participating laboratories were increased to 89, by 11.3% increase comparing with the previous year. Response rates were 100.0% for both trials just like the previous year. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.8 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, phenytoin, carbamazepine, theophylline, and phenobarbital which were peformed in more than 71% of participating laboratories, followed by cyclosporine, lithium, tacrolimus, vancomycin, methotrexate, amikacin, gentamycin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The most widely used TDM analyzer was Abbott TDx/TDxFLx (41.6%), followed by Roche Cobas Integra (21.3%), and Abbott AxSym (20.2%). The inter-laboratory coefficients of variations were not greatly improved comparing with previous years. We also determined cyclosporine and tacrolimus with reference method using liquid chromatography-tandem mass spectrometry. In conclusion, the TDM external quality assessment of 2004 showed grossly similar pattern comparing with those of previous year, except the 11.3% increase of participating laboratories.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring* ; Gentamicins ; Korea* ; Lithium ; Mass Spectrometry ; Methotrexate ; Pathology, Clinical ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2003. Number of participating laboratories were 80 which is similar to those of the previous year. Response rates were elevated to 100.0% for both trials. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 7.0 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, phenytoin, carbamazepine, theophylline, and phenobarbital, which were peformed in more than 75% of participating laboratories, followed by cyclosporine, lithium, methotrexate, tacrolimus, vancomycin, amikacin, gentamycin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The most widely used TDM analyzer was Abbott TDx/TDxFLx (52%), but its proportion were decreased slightly comparing with the previous years. The interlaboratory coefficients of variations were not greatly improved comparing with previous years. In conclusion, the TDM external quality assessment of 2003 showed grossly similar pattern comparing with those of previous year, except that the response rate was elevated to 100% and two levels of control material were used in each trials.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring* ; Gentamicins ; Korea* ; Lithium ; Methotrexate ; Pathology, Clinical ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

Three trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2002. Participating laboratories were 79 similar to the previous year. Response rates were 96.3% for 1st, 2nd, and third trials. In the first trial, 20 test items among 27 ones were responded from as least from one laboratory as follows: acetaminophen, amikacin, amitriptyline, carbamazepine, cyclosporine, digoxin, free phenytoin, gentamicin, lithium, methotrexate, phenobarbital, phenytoin, primidone, quinidine, salicylate, tacrolimus (FK-506), theophylline, tobramycin, valproic acid and vancomycin. In the second and third trial, the test items were same with those of 1st trial except the exclusion of quinidine. We included tacrolimus with a whole blood control material in addition to cyclosporine from the first trial. The most common test items were valproic acid, digoxin, phenytoin, carbamazepine, theophylline, and phenobarbital which were peformed in more than 77% of participating laboratories. The most widely used TDM analyzer was Abbott TDx/TDxFLx (56%), but its proportion were decreased slightly comparing with the previous years. In conclusion, we added tacrolimus from the year of TDM proficiency testing in 2002 and found grossly similar pattern comparing with those of previous years.
Acetaminophen ; Amikacin ; Amitriptyline ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring* ; Gentamicins ; Korea* ; Lithium ; Methotrexate ; Pathology, Clinical ; Phenobarbital ; Phenytoin ; Primidone ; Quinidine ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin

PURPOSE: Hyperhomocysteinemia was observed in epileptic patients receiving anticonvulsants, especially homozygotes for mtehylenetetrahydrofolate reductase (MTHFR) gene 677C->T mutation. Hyperhomocysteinemia induce atherosclerosis, fetal anticonvulsant syndrome, etc. Therefore, we examined any other factors that might affect the level of homocysteine in epileptic patients. METHODS: We investigated the plasma total homocysteine level in 145 patients with epilepsy. And then we analyzed various factors (clinical findings, neuro-image finding, drugs, MTHFR gene, serum folate and vitamin B12 level) affecting the level of homocysteine. RESULTS: Among the various factors, male, present neurological deficits, frequent seizure attacks, MTHFR gene 677 TT genotype, polypharmacy, and conventional drug (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone, benzodiazpines) than new drug (lamotrigine, vigabatrin, topiramate, oxcarbazepine zonisamide) were related with elevated homocysteine levels. CONCLUSION: We recommend monotherapy with new drugs and higher vitamin requirement in the male epileptic patients of MTHFR TT genotype with neurological deficits and frequent seizure attacks.
Anticonvulsants ; Atherosclerosis ; Carbamazepine ; Epilepsy ; Folic Acid ; Genotype ; Homocysteine* ; Homozygote ; Humans ; Hyperhomocysteinemia ; Male ; Oxidoreductases ; Phenobarbital ; Plasma ; Polypharmacy ; Primidone ; Seizures ; Valproic Acid ; Vigabatrin ; Vitamin B 12 ; Vitamins