Therapeutisches Drug Monitoring

Title Summary Year
High Dose Lopinavir/Ritonavir Does Not Lead to Sufficient Plasma Levels to Inhibit SARS-CoV-2 in Hospitalized Patients With COVID-19 Due to the high EC50 of SARS-CoV-2 and the fact that LPV/RTV is highly protein bound, it seems unlikely that LPV/RTV exhibits a relevant antiviral effect against SARS-CoV-2 in vivo. MassTox Series A was used for the determination of the drugs. 2021
Comparing posaconazole and itraconazole for antifungal prophylaxis in critically ill lung transplant recipients: efficacy and plasma concentrations The findings suggest that posaconazole should be used instead of itraconazole for systemic prophylaxis in critically ill lung transplant recipients. Both analytes were determined with MassTox Series A 2021
Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole The majority of patients achieved s-isavuconazole levels well within the therapeutic range with less intra/interindividual CV than patients receiving voriconazole. Drug concentrations were measured with an HPLC assay from Chromsystems. 2021
Simultaneous quantification of seven repurposed COVID-19 drugs remdesivir (plus metabolite GS-441524), chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin by a two-dimensional isotope dilution LC-MS/MS method in human serum The paper describes a multi-analyte LC-MS/MS method for the quantification of repurposed COVID-19 drugs in human serum. It uses the column of Series A in combination with calibrators and controls for the COVID-19 drugs from Chromsystems. 2021
Drug–drug interaction between itraconazole capsule and efavirenz in adults with HIV for talaromycosis treatment Concomitant administration of itraconazole capsule with efavirenz significantly reduced itraconazole and hydroxyitraconazole exposures. The clinical impact of this drug–drug interaction on talaromycosis treatment or prophylaxis in the era of potent ART needs further evaluation. Itraconazole and hydroxyitraconazole were measured with MassTox Series A 2021
Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support. Antbiotics were measured with the Chromsystems HPLC assay.  2020
Application Note: Therapeutic Drug Monitoring of COVID-19 Drugs with Components of a Commercial Assay This protocol shows that MassTox® TDM Series A can be employed for the determination of 9 COVID-19 drug candidates/metabolites in serum/plasma. Laboratories that have already MassTox® TDM Series A in operation can simply use the same chromatographic set up, sample prep and MasterColumn® A. 2020
Aneurysmal Subarachnoid Hemorrhage: Impact on Phenytoin Permeability across the Blood–Brain Barrier There is a definite decrease in the penetration of phenytoin to the brain in patients with grade 3 and 4 following aneurysmal subarachnoid hemorrhage. Phenytoin was measured with MassTox Series A 2020
Distribution of Psychotropic Drugs Into Lipoproteins The present results indicate that psychotropic drugs with certain
characteristics bind to LDL/VLDL in blood. This further implies that lipoproteins could play
an important role in drug transport. Drugs were measured with MassTox Series A Calibrator Sets 
2019
Short communication: Distribution of psychotropic drugs into lipoproteins The present results indicate that psychotropic drugs with certain characteristics bind to LDL/VLDL in blood. This further implies that lipoproteins could play an important role in drug transport.. Measured with MassTox TDM Series A 2019
Interindividual and Intraindividual Variation of Methylphenidate Concentrations in Serum and Saliva of Patients With Attention-Deficit/Hyperactivity Disorder Data indicate that the interindividual variation in saliva to serum concentrations is rather high, whereas the intraindividual variation is fairly low. Methylphenidate and ritalinic acid were measured with MassTox TDM Series A.  2018
Serum and Saliva Concentrations of Venlafaxine, O-Desmethylvenlafaxine, Quetiapine, and Citalopram in Psychiatric Patients Saliva therapeutic drug monitoring of psychoactive drugs might become a useful approach to achieving individual treatment regimens. Drugs were measured with MassTox TDM Series A.  2018
The effect of serum levetiracetam concentrations on therapeutic response and IL1-beta concentration in patients with epilepsy Monitoring LEV Cmax values may enhance LEV adherence because patients would be less likely to develop adverse effects. LEV was measured with MassTox TDM Series A.  2018
Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability Considering the percentage of therapeutic azole plasma trough levels and the intrapatient variability, posaconazole tablets seem to be the most reliable choice of antimycotic therapy in lung transplant recipients. MassTox TDM Series A was used with antimycotics parameter set.  2017
Correlation of CYP2C19 genotype with plasma voriconazole levels: a preliminary retrospective study in Indians. The HPLC assay from Chromsystems has been used in clinical research  2015
Effects of Antiepileptic Drug Monotherapy on One-Carbon Metabolism and DNA Methylation in Patients With Epilepsy The findings suggest that the effects of AED monotherapy on one-carbon metabolism may induce specific regions of DNA hypomethylation. Valproate and lamotrigine was measured by HPLC  2015
Effects of Antiepileptic Drug Monotherapy on One-Carbon metabolism and DNA Methylation in Patients with Epilepsy The findings suggest that the effects of AED monotherapy on one-carbon metabolism may induce specific regions of DNA hypomethylation. Chromsystems HPLC was used for the determination of valproic acid and lamotrigine. 2015
Carbamazepine Clearance and Seizure Stability During Pregnancy Carbamazepine monotherapy may be a relatively safe and cost effective treatment option for women with focal epilepsy syndromes during pregnancy. Carbamazepine and ist epoxide was measured by the Chromsystems HPLC assay 2014
Carbamazepine clearance and seizure stability during pregnancy. Chromsystems HPLC used in clinical research 2014
Midazolam Pharmacokinetics in Morbidly Obese Patients Following Semi-Simultaneous Oral and Intravenous Administration: A Comparison With Healthy Volunteers In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased.  The MassTox Series A assay was used for midazolam 2014
MODEL-BASED LAMOTRIGINE CLEARANCE CHANGES DURING PREGNANCY: CLINICAL IMPLICATION An increase in changes in the oral clearence of lamotrigine may correspond to decreases in lamotrigine  blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Lamotrigine was measured by HPLC with an Chromsystems assay.  2014
THERAPEUTIC DRUG MONITORING OF IMATINIB IN GIST PATIENTS Feasibility Study for TDM of imatinib that was measured by HPLC.   2014
Ziprasidone as adjunctive therapy in severe bipolar patients treated with clozapine Aim of the study was to confirm the efficacy and tolerability of ziprasidone as adjunctive therapy in bipolar patients partially responding to clozapine or with persisting negative symptoms, overweight, or with metabolic syndrome. Clozapine and active metabolites were measured with an HPLC assay from Chromsystems 2014
Assessment of Hepatic Detoxification Activity: Proposal of an Improved Variant of the (13)c-methacetin Breath Test Levetiracetam was measured by a Chromsystems HPLC assay in this clinical study.   2013
Potential Factors for Inadequate Voriconazole Plasma Concentrations in Intensive Care Unit Patients and Patients With Hematological Malignancies In conclusion, potential factors like younger age, prophylaxis, underlying hematological malignancy, BMI, and concomitant PPI should be considered within the algorithm of voriconazole treatment.Voriconazole plasma concentrations were measured with an HPLC assay.  2013
Poster: Therapeutic Drug Monitoring of Antiepileptic Drugs During Pregnancy Clearance changes during pregnancy can lead to sub-therapeutic plasma levels of the AEDs. Pregnancy thus warrants a special case for the TDM of these medications As the numbers of these drugs seems to be ever increasing, a multiplexed assay strategy for their measurement seems appropriate. 2013
Population pharmacokinetics of lamotrigine in Chinese children with epilepsy A PPK model of lamotrigine (LTG) in Chinese children with epilepsy was successfully established with NONMEM. LTG concentrations can be predicted accurately by this model. The model may be very useful for establishing initial LTG dosage guidelines. LTG was measured with Chromsystems HPLC assay.  2012
Augmentation of Clozapine With Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study . A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation, according to the study that used a Chromsystems HPLC for the determination of clozapone and its metabolites.  2010
Title Summary Year
Simultaneous quantification of seven repurposed COVID-19 drugs remdesivir (plus metabolite GS-441524), chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin by a two-dimensional isotope dilution LC-MS/MS method in human serum The paper describes a multi-analyte LC-MS/MS method for the quantification of repurposed COVID-19 drugs in human serum. It uses the column of Series A in combination with calibrators and controls for the COVID-19 drugs from Chromsystems. 2021
Interpretation of tandem mass spectra of antiepileptic drugs using accurate-m/z data and m/z-shifts with stable-isotope labeled analogues This review helps in strengthening our understanding of the small-molecule fragmentation in MS–MS. In the case of AEDs, the structure proposals for the product ions can not only be confirmed with accurate-m/z data from high-resolution MS instruments, but also by studying m/z-shifts of products ions of the stable-isotope labeled analogues, that are frequently used as internal standard. 2020
Lack of concordance between EMIT assay and LC-MS/MS for Therapeutic Drug Monitoring of Mycophenolic Acid: Potential increased risk for graft rejection? This study highlights a clinically relevant systematic overestimation of MPA concentration by EMIT, supporting the switch to LC–MS/MS techniques for TDM purpose. MPA was measured with the MassTOX Series A assay. 2020
Where clinical chemistry meets medicinal chemistry. Systematic analysis of physico-chemical properties predicts stability of common used drugs in gel separator serum tubes For ease of handling and minimization of blood drawing times, the authors assume that tubes containing separator gel can be used for therapeutic drug monitoring of high hydrophilic drugs. In contrast lipophilic compounds showing logP higher than 3 and/or CF>20 should be critically considered and validated by extensive stability studies. Concentrations of selected drugs were measured with MassTox TDM Series A, AED parameter set.  2019
Poster: Inter- and intraindividual variations of methylphenidate in serum and oral fluid of ADHD patients The LC-MS/MS kit MassTox TDM Parameter Set Antidepressants 2/Psychostimulants is suitable and reliable for the
determination of methylphenidate and ritalinic acid in oral fluid.
Measured serum concentration values for methylphenidate correspond to the previously published data.
2016
Poster: Methylphenidate and ritalinic acid determination in serum and saliva from patients with attention deficit hyperactivity disorder The MassTox® TDM Parameter Set Antidepressants from Chromsystems is methodologically and analytically suitable for the determination of MPH and its main metabolite RA in serum/plasma as well as saliva by LC-MS/MS. This allows a substantially simplified form of drug monitoring in pediatric pharmacotherapy. Measured serum concentrations for methylphenidate correspond with the usual and published data 2014

Please find here publications as guides for reference ranges or therapeutic ranges. As they may differ from other published data. Data vary depending on patient population and measurement method, please determine ranges for your laboratory. When determining ranges make sure that you comply with local national requirements. 

Title Summary Year
Gressner A.M., Arndt T. (Eds). Lexikon der Medizinischen Laboratoriumsdiagnostik, 3rd edition, Springer Verlag (2019).   Book with a number of reference values (German).  2019
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Guidelines for therapeutic drug monitoring in psychatriy. 2017
Ludewig, Regenthal (ed). Akute Vergiftungen und Arzneimittelüberdosierungen. 11th editiion, WVG Stuttgart (2015). Book with reference ranges (German).  2015
Therapeutic and toxic blood concentrations ofnearly 1000 drugs and other xenobiotics.  Rerefence values for a number of drugs  2012
Thomas L. (ed)- Labor und Diagnose, 8th edition, TH books (2012) Book with reference ranges. 2012
AGNP Consensusguidelines for therapeutic drug monitoring in psychiatry: Update  Guidelines for therapeutic drug monitoring in psychatriy 2011
Antifungal therapeutic drug monitoring: established and emergingindications.  reference values for antifungal drugs 2009
Therapeutic drug monitoringof old and newer anti-epileptic drugs Reference values for anti-apileptic drugs 2004
Therapeutic and toxic blood concentrations of more than 800 drugs and otherxenobiotics.  Rerefence values for a number of drugs  2003
Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation:importance of mycophenolic acid therapeutic drug monitoring. Reference values for MPA 1999