Therapeutic Drug Monitoring - TDM

Therapeutic drug monitoring (TDM) refers to the clinical practice of measuring drugs and/or metabolites in blood or serum/plasma at a specific time point to determine if a patient’s drug concentrations are within the therapeutic range, and are neither subtherapeutic nor potentially toxic. The purpose of TDM is to optimize dosing to target a therapeutic plasma drug concentration while minimizing toxicity.

Tabs Content

Clinical Overview

Quick Answers

What is the purpose of therapeutic drug monitoring (TDM)?

Effective drug treatment is dependent on patient adherence/compliance to prescribed medications. Drug treatment and dosage should be personalized for each patient due to interindividual variability in response to therapy. TDM allows for personalization of drug selection and dose, evaluation of adherence, and investigation of changes in pharmacokinetics (eg, drug-drug interactions).

When should TDM testing be performed?

Therapeutic drug monitoring should be performed once the patient has achieved steady-state concentration, and when there are changes to drug therapy and/or changes in response (eg, toxicity).

What specimens are appropriate for TDM?

Whole blood, serum, and plasma specimens can be used to assess if drug dosage avhieved the targeted therapeutic range and patient adherence. Urine specimens can be used to assess patient adherence to medication by detecting parent drug and metabolites.

How should results be interpreted?

Drug results should be interpreted relative to the established therapeutic range, dose-related range, or toxic range (if applicable), timing of specimen collection (eg, predose [trough], peak, or random), specimen type, and the patient’s clinical response to treatment. Results can be affected by several variables. Incorrect timing of specimen collection relative to the therapeutic range can be misleading. Response to drug therapy is also influenced by the patient’s pharmacogenetics (eg, normal, rapid, or poor drug metabolism), physical conditions (eg, pregnancy, comorbidities), and drug-drug or food-drug interactions that could lead to an increase, decrease, or inhibited response to therapy.

Indications for Testing

Not all medications require TDM, especially when the drug has a wide therapeutic index or low risk for severe adverse effects. TDM is utilized for drugs that have

Known relationship between dose and blood/serum/plasma concentrations
Narrow therapeutic window
High patient variability in pharmacokinetics (eg, drug liberation, absorption, distribution, metabolism, and elimination)
Severe adverse effects (dose related)

TDM is also used to

Identify drug-drug or food-drug interactions
Monitor patient compliance
Monitor status during decontamination or detoxification
Monitor changes in drug concentrations related to aging, pregnancy, or clinical status

TDM should be performed once a drug has reached steady state concentration.

Specimen Selection

Therapeutic and toxic ranges are typically established in the following specimen types: serum, plasma, and whole blood.

Serum/Plasma and Whole Blood

Clinical signs and symptoms of effective drug treatment, ineffective drug treatment, and toxicity may correlate with drug and/or metabolite concentrations in serum, plasma, and/or whole blood.

Serum, plasma, or whole blood specimens are also appropriate for

Patients on dialysis
Suspected cases of malabsorption (eg, gastric bypass)
Evaluating other aspects of an individual patient’s pharmacokinetics

Whole Blood

Whole blood specimens are used for TDM of select drugs such as immunosuppressive drugs (eg, cyclosporine A, tacrolimus, everolimus, sirolimus, and thiopurine drugs) due to drug accumulation in RBCs.

Oral Fluid (Saliva)

Oral fluid drug concentrations tend to correlate to serum/plasma concentrations. The window of drug detection is about 1-2 days after drug use; therefore, oral fluid can be used to detect recent drug exposure. Therapeutic ranges are not well established in oral fluid.

Urine

Urine drug and metabolite concentrations do not correlate with signs and symptoms of drug therapy or toxicity; therefore, urine should not be a specimen collected for TDM. Urine drug concentrations should also not be used to extrapolate the dose that was administered.

Timing of Specimen Collection

Therapeutic ranges are typically established at the following timed blood collections after steady state concentrations have been reached (generally 5-7 half-lives after initiation of or change in dosing).

Trough or predose (0-60 minutes before dose administration)
Peak (generally 1-2 hours after drug administration; however, this is highly drug dependent)
Randomly

Commonly Used Testing Strategy

Quantitative testing for TDM may be performed by immunoassay, high performance liquid chromatography (HPLC), or mass spectrometry. Drug results that are reported as less than the assay cutoff should be interpreted as “not detected.”

Frequently Asked Questions

What is the definition of half-life?

The half-life of a drug refers to the time it takes for 50% of the drug to be eliminated from blood.

What is the definition of steady-state concentration?

Steady-state concentration occurs when the rate of drug administration is equal to the rate of elimination. Generally, steady-state concentration can be achieved after patient has consistently administered the drug for the duration of 5-7 half-lives (eg, if a drug has a half-life of 24 hours and is administered once a day, then steady-state concentration can be achieved after 5-7 days of drug administration).

What is the window of detection of drugs in blood, serum, or plasma specimens?

In general, the window of detection in blood, serum, and plasma is 1-2 days after drug administration.

The window of detection for drugs is dependent on several factors, including the following

Half-life of the drug
Drug dose
Frequency of drug administration
Route of administration
Drug formulation
Chemistry of the drug (eg, water soluble vs lipid soluble, stability)
Patient’s age
Patient’s body composition and sex
Patient’s pathophysiology and pharmacokinetics
Coadministration of other medications
Hydration and nutrition status
Analytical limitations of testing

Can gel separator tubes be used for toxicology testing?

Gel separator tubes are not recommended for testing in toxicology. Drugs that are lipid soluble may be absorbed into the gel and may cause a falsely low drug result.

ARUP Lab Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Monitor levels of antimicrobial drug

Antibiotic Level, Aztreonam 0060845

Method: Quantitative Bioassay

Normal peak serum concentration:

90-164 µg/mL with a 1 g IV dose
204-255 µg/mL with a 2 g IV dose

Antibiotic Level, Ceftazidime 2004886

Method: Bioassay

Normal peak serum concentration:

42 µg/mL with a 500 mg IV dose
69 µg/mL with a 1 g IV dose
159-186 µg/mL with a 2 g IV dose

Antibiotic Level, Meropenem 0060844

Method: Quantitative Bioassay

Normal peak serum concentration:

26 µg/mL with a 500 mg IV dose
55-62 µg/mL with a 1 g IV dose

Antibiotic Level, Nafcillin 0060843

Method: Quantitative Bioassay

Normal peak serum concentration:

7.7 µg/mL with a 1 g PO dose
7.6 µg/mL with a 1 g IM dose
40 µg/mL with a 500 mg IV dose

Antibiotic Level, Piperacillin 0060842

Method: Quantitative Bioassay

Normal peak serum concentration:

389-484 µg/mL with a 4 g IV dose of piperacillin
209 µg/mL with a 3.375 g IV dose of piperacillin/tazobactam
224 µg/mL with a 4.5 g IV dose of piperacillin/tazobactam

Antibiotic Level, Ticarcillin 0060841

Method: Quantitative Bioassay

Normal peak serum concentration: 324 µg/mL with a 3.1 g IV dose of ticarcillin/clavulanate

Optimize drug therapy and monitor patient adherence

Gentamicin, Peak Level 0090305

Method: Immunoassay

Optimal: 5.0-10.0 µg/mL
Toxic: <12.0 µg/mL

Gentamicin, Trough Level 0090310

Method: Immunoassay

Optimal: 0.5-2.0 µg/mL
Toxic: >2.0 µg/mL

Sulfonamides (Sulfas) 0020044

Method: Quantitative Colorimetry

Therapeutic range: 5-15 mg/dL
Toxic: >20 mg/dL

Vancomycin, Peak Level 0090325

Method: Immunoassay

Optimal: 30.0-40.0 µg/mL
Toxic: ≥80.1 µg/mL

Vancomycin, Random Level 0090285

Method: Fluorescence Polarization Immunoassay

Trough level optimal: 10.0-20.0 µg/mL

Peak level optimal: 30.0-40.0 µg/mL

Vancomycin, Trough Level 0090330

Method: Immunoassay

Optimal: 10.0-20.0 µg /mL

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Carbamazepine Epoxide and Total 0092211

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Carbamazepine-10,11 Epoxide

Toxic: >15 µg/mL

Total carbamazepine

Therapeutic range: 4-12 µg/mL
Toxic: >15 µg/mL

Carbamazepine, Free and Total, Serum or Plasma 2011763

Method: Quantitative Enzyme Multiplied Immunoassay Technique

Total carbamazepine

Therapeutic range: 4-12 µg/mL
Toxic: >15 µg/mL

Free carbamazepine

Therapeutic range: 1-3 µg/mL
Toxic: >3.8 µg/mL

Percent free carbamazepine: 8-35%

Carbamazepine, Total 0090260

Method: Immunoassay

Therapeutic range: 4-12 µg/mL

Toxic: >15 µg/mL

Clobazam Quantitative, Serum or Plasma 2008597

Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Ethosuximide, Serum or Plasma 2010358

Method: Quantitative Enzyme Immunoassay

Therapeutic range: 40-100 µg/mL
Toxic: >150 µg/mL

Felbamate 0094030

Method: Quantitative High Performance Liquid Chromatography

Toxic: >200 µg/mL

Gabapentin 0090057

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 2-20 µg/mL

Keppra (Levetiracetam) 0098627

Method: Quantitative Enzyme Immunoassay

Therapeutic range: 12-46 µg/mL

Lacosamide, Serum or Plasma 2003182

Method: High Performance Liquid Chromatography/Tandem Mass Spectrometry

Therapeutic range: suggested range 5-10 µg/mL
Dose-related range: 2.5-18 µg/mL

Lamotrigine 0090177

Method: Quantitative Enzyme Immunoassay

Therapeutic range: 2.5-15 µg/mL

Methsuximide Metabolite, Serum or Plasma 3000251

Method: Quantitative High Performance Liquid Chromatography

Component: normethsuximide

Therapeutic range: 10-40 µg/mL

Oxcarbazepine or Eslicarbazepine Metabolite (MHD) 0098834

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 3-35 µg/mL

Toxic: >40 µg/mL

Perampanel Quantitative, Serum or Plasma 2013025

Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Phenobarbital 0090230

Method: Immunoassay

0-2 months:

Therapeutic range: 15-30 µg/mL
Toxic: ≥40.1 µg/mL

3 months and older:

Therapeutic range: 15-40 µg/mL
Toxic: ≥50.1 µg/mL

Phenobarbital, Total/Free/Bound, Serum or Plasma 0091551

Method: Quantitative High Performance Liquid Chromatography

Pregabalin, Serum or Plasma 2011609

Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Rufinamide, Serum or Plasma 2003176

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Dose-related range: 3-30 µg/mL

Tiagabine, Serum or Plasma 0091541

Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Topiramate 0070390

Method: Quantitative Enzyme Immunoassay

Therapeutic range: 5-20 µg/mL

Valproic Acid 0090290

Method: Fluorescence Polarization Immunoassay

Toxic: ≥151 µg/mL

Vigabatrin Quantitative, Serum or Plasma 2011039

Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Zonisamide 0097908

Method: Quantitative Enzyme Multiplied Immunoassay Technique

Toxic: >80 µg/mL

Preferred test for therapeutic drug management in patients with renal failure or conditions that may alter albumin concentrations

Phenytoin, Free and Total 0090141

Method: Quantitative Enzyme Multiplied Immunoassay Technique

Total phenytoin

Therapeutic range: 10-20 µg/mL
Toxic: >30 µg/mL

Free phenytoin

Therapeutic: 1-2.5 µg/mL
Toxic: >2.5 µg/mL

Percent free phenytoin: 8-14%

Valproic Acid, Free and Total 0099310

Method: Quantitative Enzyme Multiplied Immunoassay Technique

Total valproic acid:

Therapeutic range: 50-125 µg/mL
Toxic: >150 µg/mL

Free valproic acid:

Therapeutic range: 7-23 µg/mL
Toxic: >30 µg/mL

Percent free valproic acid: 5-18%

Therapeutic drug management for patients with renal failure or conditions that may alter albumin concentrations

Phenytoin, Free 2010481

Method: Quantitative Enzyme Multiplied Immunoassay Technique

Therapeutic range: 1-2.5 µg/mL
Toxic: >2.5 µg/mL

Optimize drug therapy and monitor patient adherence

This test can be ordered when fosphenytoin is administered

Phenytoin 0090090

Method: Enzyme Immunoassay

0-2 months:

Therapeutic: 6-14 µg/mL
Toxic: ≥14.1 µg/mL

3 months and older:

Therapeutic: 10-20 µg/mL
Toxic: ≥30.1 µg/mL

Optimize drug therapy and monitor patient adherence

The active metabolite of primidone is phenobarbital

Primidone and Metabolite 0090202

Method: Immunoassay

Phenobarbital
0-2 months:

Therapeutic range: 15-30 µg/mL
Toxic: ≥40.1 µg/mL

3 months and older:

Therapeutic range: 15-40 µg/mL
Toxic: ≥50.1 µg/mL

Primidone (Mysoline)
Reference interval: 5-12 µg/mL

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Tricyclic Antidepressants, Quantitative, Serum or Plasma 2007549

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Drugs tested, therapeutic ranges/toxic levels:

Amitriptyline (Elavil, Vanatrip): therapeutic range/toxic level not established
Nortriptyline (Aventyl, Pamelor): therapeutic range, 50-150 ng/mL; toxic, >500 ng/mL
Total amitriptyline and nortriptyline: therapeutic range, 95-250 ng/mL; toxic, >500 ng/mL
Imipramine (Tofranil): therapeutic range/toxic level not established
Desipramine (Norpramin): therapeutic range, 100-300 ng/mL; toxic, >500 ng/mL
Total imipramine and desipramine: therapeutic range, 150-300 ng/mL; toxic, >500 ng/mL
Doxepin (Sinequan, Zonalon): therapeutic range/toxic level not established
Nordoxepin: therapeutic range/toxic level not established
Total doxepin and nordoxepin: therapeutic range, 100-300 ng/mL; toxic, >500 ng/mL
Protriptyline (Vivactil): therapeutic range, 70-240 ng/mL; toxic, >400 ng/mL
Clomipramine (Anafranil): therapeutic range/toxic level not established
Norclomipramine: therapeutic range/toxic level not established
Total clomipramine and norclomipramine: therapeutic range, 220-500 ng/mL; toxic, >900 ng/mL

Amitriptyline and Nortriptyline, Serum or Plasma 0090158

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range (total): 95-250 ng/mL
Toxic: >500 ng/mL

Bupropion, Serum or Plasma 2010357

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 50-100 ng/mL
Toxic: >400 ng/mL

Clomipramine and Metabolite, Serum or Plasma 0099336

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range (total): 220-500 ng/mL
Toxic: >900 ng/mL

Doxepin and Metabolite, Serum or Plasma 0090102

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range (total): 100-300 ng/mL
Toxic: >500 ng/mL

Fluoxetine and Metabolite Quantitative, Serum or Plasma 2014180

Method: Quantitative Gas Chromatography/Mass Spectrometry (GC/MS)

Imipramine and Desipramine, Serum or Plasma 0090157

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range (total): 150-300 ng/mL
Toxic: >500 ng/mL

Nortriptyline 0090074

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 50-150 ng/mL
Toxic: >500 ng/mL

Protriptyline, Serum or Plasma 0090106

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 70-240 ng/mL
Toxic: >400 ng/mL

Sertraline 0098745

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Toxic: >300 ng/mL

Trazodone 0090316

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 0.5-2.5 µg/mL
Toxic: >4 µg/mL

Venlafaxine and Metabolite, Serum or Plasma 2007957

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range (total): 195-400 ng/mL

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Fluconazole, Quantitative by LC-MS/MS 0097621

Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 5-20 µg/mL

Itraconazole, Quantitative by LC-MS/MS 0098519

Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic ranges:

Itraconazole, localized infection: >0.5 µg/mL
Itraconazole, systemic infection: >1.0 µg/mL

Posaconazole, Quantitative by LC-MS/MS 2001739

Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: >0.7 µg/mL

Voriconazole, Quantitation by LC-MS/MS 2001737

Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 1-6 µg/mL
Toxic: >6 µg/mL

The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Schizophrenia topic.)

Optimize drug therapy and monitor patient adherence

Aripiprazole and Metabolite, Serum or Plasma 2007945

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: not well established

Total (aripiprazole and dehydroaripiprazole): 150-500 ng/mL

Chlorpromazine 0090870

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range:

Child (0-11 yrs): 30-80 ng/mL
Adult (≥12 yrs): 50-300 ng/mL

Toxic level

Child (0-11 yrs): >200 ng/mL
Adult (≥12 yrs): >750 ng/mL

Clozapine and Metabolites, Serum or Plasma, Quantitative 2013433

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Toxic: ≥1500 ng/mL

Fluphenazine 0099906

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 0.5-2 ng/mL

Haloperidol 0099640

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 5-20 ng/mL
Toxic: >42 ng/mL

Lurasidone Quantitative, Serum or Plasma 2013018

Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Olanzapine 0098833

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 20-80 ng/mL

Paliperidone, Serum or Plasma 2007949

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Proposed dose-related range: 20-60 ng/mL

Perphenazine, Serum or Plasma (INACTIVE as of 11/12/18) 2011555

Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Therapeutic range: 0.6-2.4 ng/mL
Toxic: >12 ng/mL

Quetiapine, Serum or Plasma 2003118

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Predose draw (trough) preferred:

Therapeutic range: 70-170 ng/mL
Toxic: >1000 ng/mL

Peak draw (1.5 hour postdose) not recommended:

Therapeutic range: 100-1000 ng/mL
Toxic: >1500 ng/mL

Risperidone and Metabolite, Serum or Plasma 2007951

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: not well established

Total (risperidone and metabolite): 20-60 ng/mL

Thiothixene, Serum or Plasma (INACTIVE as of 11/12/18) 2011783

Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Therapeutic range: 1-15 ng/mL

Ziprasidone, Serum or Plasma (INACTIVE as of 11/12/18: Refer to 3000721 in the November Hotline) 2007955

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Proposed dose-related range: 50-200 ng/mL

Monitor patient adherence and exposure

Lithium, Serum or Plasma 0020038

Method: Colorimetry

Therapeutic range: 0.5-1.2 mmol/L
Toxic: 1.6 or greater mmol/L

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Amiodarone and Metabolite 0090161

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range (total): 0.5-2 µg/mL
Toxic (total): >3 µg/mL

Flecainide 0090003

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 0.20-1 µg/mL
Toxic: >1.50 µg/mL

Optimize drug therapy and monitor patient adherence

Does not measure digoxin (Lanoxin, Digitek); for digoxin testing, order digoxin test

Digitoxin 0090085

Method: Quantitative CEDIA Immunoassay

Therapeutic range: 10-30 ng/mL
Toxic: >45 ng/mL

The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Immunosuppressive Drug Optimization and Monitoring topic.)

Optimize drug therapy and monitor patient adherence

Cyclosporine A by Tandem Mass Spectrometry 0070035

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 100-400 ng/mL

Kidney transplant (in combination with Everolimus)

1 mo posttransplant: 100-200 ng/mL
2-3 mos posttransplant: 75-150 ng/mL
4-5 mos posttransplant: 50-100 ng/mL
6-12 mos posttransplant: 25-50 ng/mL

Heart transplant

Up to 3 mos posttransplant: 350-525 ng/mL
4 mos and older posttransplant: 145-350 ng/mL

Liver transplant: 290-525 ng/mL

Toxic: >700 ng/mL

Cyclosporine A, 2-Hour Post Dose (C2) by Tandem Mass Spectrometry 0058902

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Renal transplant (suggested target range): 800-1700 ng/mL

Liver transplant (suggested target range): 600-1000 ng/mL

Everolimus by Tandem Mass Spectrometry 0092118

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Kidney transplant (in combination with Cyclosporine): 3-8 ng/mL

Liver transplant (in combination with Tacrolimus): 3-8 ng/mL

Toxic value: >15 ng/mL

Mycophenolic Acid and Metabolites 2010359

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Mycophenolic acid

Therapeutic range: 1-3.5 µg/mL
Toxic: >25 µg/mL

Mycophenolic acid glucuronide

Therapeutic range: 35-100 µg/mL

Sirolimus by Tandem Mass Spectrometry 0098467

Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Kidney transplant (in combination with Cyclosporine) therapeutic range: 4-12 ng/mL

Toxic: >25 ng/mL

Tacrolimus by Tandem Mass Spectrometry 0090612

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range

Kidney transplant

0-3 mos posttransplant: 7-20 ng/mL
3 mos and older: 5-15 ng/mL

Heart transplant

0-3 mos posttransplant: 10-20 ng/mL
3 mos and older: 5-15 ng/mL

Liver transplant

1-12 mos posttransplant: 5-20 ng/mL

Toxic: >25 ng/mL

Therapeutic monitoring and evaluating full elimination of the drug (eg, toxicity, pregnancy)

Leflunomide Metabolite, Serum or Plasma 2007460

Method: High Performance Liquid Chromatography/Mass Spectrometry

Therapeutic range: >40.000 µg/mL

Phenotype test to assess risk for severe myelosuppression with standard dosing of thiopurine drugs

Use for individuals being considered for thiopurine therapy

Must be performed before thiopurine therapy is initiated

Can also detect rapid metabolizer phenotype

Thiopurine Methyltransferase, RBC 0092066

Method: Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Normal TPMT activity: 24-44 U/mL

Low risk of bone marrow toxicity; no dose adjustment recommended

Intermediate TPMT activity: 17-23.9 U/mL

Intermediate risk of bone marrow toxicity; dose reduction and therapeutic drug management recommended

Low TPMT activity: <17 U/mL

High risk of bone marrow toxicity; avoid thiopurine drugs

High TPMT activity: >44 U/mL

No risk for bone marrow toxicity; may require higher than normal standard dose

Therapeutic drug management recommended

The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Pain and Addiction Management topic.)

Aid in the assessment of acetaminophen toxicity

Acetaminophen 0090001

Method: Spectrophotometry

Critical values:

Post 4-hour ingestion: >150 µg/mL
Post 12-hour ingestion: >40 µg/mL

Optimize drug therapy and monitor patient adherence

Ibuprofen Quantitative, Serum or Plasma 2014183

Method: Quantitative High Performance Liquid Chromatography

Aid in assessment of the etiology of anion gap acidosis

Salicylate Assay 0090251

Method: Spectrophotometry

Analgesic: 2-10 mg/dL
Anti-inflammatory: 10-30 mg/dL
Toxic: ≥31 mg/dL or greater

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize dose, detect variable pharmacokinetics, and monitor patient adherence

Imatinib 3000539

Method: Immunoturbidimetry

Therapeutic range:

Chronic myelogenous leukemia: >1000 ng/mL
Gastrointestinal stromal tumor: >1100 ng/mL

Monitor methotrexate concentration

Methotrexate, Sensitive 2005405

Method: Quantitative Immunoassay

Low dose: 0.50-1.00 µmol/L

High dose:

24 hrs: ≤5.00 µmol/L
48 hrs: ≤0.50 µmol/L
72 hrs: ≤0.10 µmol/L

The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Pain and Addiction Management topic.)

Monitor patient adherence

Buprenorphine and Metabolites, Serum or Plasma, Quantitative 2012647

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 1 ng/mL

Fentanyl and Metabolite, Serum or Plasma, Quantitative 2011776

Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Therapeutic range: 0.1 ng/mL

Methadone and Metabolite, Serum or Plasma, Quantitative 0090699

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 10 ng/mL

Opiates, Serum or Plasma, Quantitative 0092354

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range 2 ng/mL for the following:

Codeine
Morphine
6-acetylmorphine
Hydrocodone
Hydromorphone
xycodone
Oxymorphone

Propoxyphene and Metabolite, Serum or Plasma, Quantitative 2010464

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Therapeutic range: 10 ng/mL

Tapentadol, Free, Serum or Plasma 3000584

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Tramadol and Metabolite, Quantitative, Serum or Plasma 2014686

Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

(eg, benzodiazepines, barbiturates, muscle relaxants)

The therapeutic range is based on serum predose (trough) draw at steady-state concentration

Optimize drug therapy and monitor patient adherence

Alprazolam 0090010

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Dose-related ranges:

Anxiety: 10-40 ng/mL (dose, 1-4 mg/d)
Phobia and panic: 50-100 ng/mL (dose, 6-9 mg/d)

Toxic: >100 ng/mL

Benzodiazepines, Serum or Plasma, Quantitative 2010445

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

See individual drug analytes for therapeutic ranges and toxic thresholds

Carisoprodol and Meprobamate, Serum or Plasma, Quantitative 2011450

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Carisoprodol, Serum or Plasma

Dose-related range: <8 µg/mL
Toxic: ≥8 µg/mL

Meprobamate, Serum or Plasma

Dose-related range: 5-20 µg/mL
Toxic: >40 µg/mL

Clonazepam 0090055

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Dose-related range: 20-70 ng/mL
Dose (Adult): 1-8 mg/d
Toxic: >80 ng/mL

Clorazepate (Assayed as Nordiazepam) 0090196

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Dose-related range: 100-1500 ng/mL (based on common dosage amounts)
Toxic: >2500 ng/mL

Diazepam and Nordiazepam 0090076

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Diazepam

Dose-related range: 200-1000 ng/mL (based on normal dosage amounts)

Nordiazepam

Dose-related range: 100-1500 ng/mL (based on normal dosage amounts)

Toxic: >2500 ng/mL

Librium and Nordiazepam 0090148

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Librium

Therapeutic range: 500-3000 ng/mL
Dose (adult): 5-100 mg
Toxic: >5000 ng/mL

Nordiazepam

Therapeutic range: 100-1500 ng/mL (based on normal dosages)
Toxic: >2500 ng/mL

Lorazepam 0090181

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Dose-related range: 50-240 ng/mL
Dose (adult): 1-10 mg/d
Toxic: >300 ng/mL

Prazepam (Assayed as Nordiazepam) 0090672

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Prazepam

Dose-related range: 20-60 mg/d

Nordiazepam

Dose-related range: 100-1500 ng/mL
Toxic: >2500 ng/mL

Optimize drug therapy and monitor patient adherence

Useful for ruling out barbiturate exposure

For follow-up testing of a presumptive result, urine barbiturates quantitative test is preferred

Barbiturates, Serum or Plasma, Quantitative 2012201

Method: Quantitative Gas Chromatography-Mass Spectrometry

See individual drug analytes for therapeutic ranges and toxic thresholds

Screening test for benzodiazapines

Results are unconfirmed and are to be used for medical (treatment) purposes only

Benzodiazepines Detection 0090367

Method: Immunoassay

Monitor patient adherence and exposure

Ketamine and Metabolite Quantitative, Serum or Plasma 0091507

Method: Quantitative Gas Chromatography-Mass Spectrometry

Detect use, optimize dose, and/or monitor patient adherence

Zolpidem, Serum or Plasma, Quantitative 2012652

Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Medical Reviewers

Johnson-Davis, Kamisha, PhD, DABCC, FAACC, Medical Director, Clinical Toxicology at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

McMillin, Gwendolyn A., PhD, Medical Director, Toxicology, and Medical Director, Pharmacogenetics, at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

References

Additional Resources

Moller M, Gareri J, Koren G. A review of substance abuse monitoring in a social services context: a primer for child protection workers. Can J Clin Pharmacol. 2010; 17(1): e177-93. PubMed

Moyer T, McMillin G. Therapeutic drugs. In Burtis CA, Ashwood ER and Burns DE, eds. Tietz Fundamentals of Clinical Chemistry, 6th ed.. MO: Saunders/Elsevier, 2008.

Moyer T, Shaw L. Therapeutic drugs and their management.. In Burtis CA, Ashwood ER and Burns DE, eds. Clinical Chemistry & Molecular Diagnostics, 4th ed. Philadelphia, PA: WB Saunders, 2005.

Riedel M, Musil R, Seemüller F, Spellmann I, Möller H, Schennach-Wolff R. Safety evaluation of zotepine for the treatment of schizophrenia. Expert Opin Drug Saf. 2010; 9(4): 659-66. PubMed

Schultz SH, North SW, Shields CG. Schizophrenia: a review. Am Fam Physician. 2007; 75(12): 1821-9. PubMed

Shin JK, Malone DT, Crosby IT, Capuano B. Schizophrenia: a systematic review of the disease state, current therapeutics and their molecular mechanisms of action. Curr Med Chem. 2011; 18(9): 1380-404. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology^®

Wong SH, Johnson-Davis KL, Garrison K, Rankin JD, Muhammad CS. Everolimus TDM using Thermo Fisher QMS immunoassay on Indiko, Beckman DxC, AU680, and AU5800 analyzers. Clin Biochem. 2017; 50(7-8): 425-430. PubMed

Wu F, Slawson MH, Johnson-Davis KL. Metabolic Patterns of Fentanyl, Meperidine, Methylphenidate, Tapentadol and Tramadol Observed in Urine, Serum or Plasma. J Anal Toxicol. 2017; 41(4): 289-299. PubMed

Educational Videos

Content Review:

January 2018

Last Update: September 2018

Therapeutic Drug Monitoring - TDM

Quick Answers

What is the purpose of therapeutic drug monitoring (TDM)?

When should TDM testing be performed?

What specimens are appropriate for TDM?

How should results be interpreted?

Indications for Testing

Specimen Selection

Serum/Plasma and Whole Blood

Whole Blood

Oral Fluid (Saliva)

Urine

Timing of Specimen Collection

Commonly Used Testing Strategy

Frequently Asked Questions

ARUP Lab Tests

Antibiotic Tests

Anticonvulsant/Antiepileptic Tests

Antidepressant Tests

Antifungal Tests

Antipsychotic Tests

Cardiovascular Drug Tests

Immunosuppressant Tests

Nonopioid Pain Medication Tests

Oncology Tests

Opiate/Opioid Analgesic Tests

Sedative-Hypnotics Tests

Medical Reviewers

References

Additional Resources

References from the ARUP Institute for Clinical and Experimental Pathology^®


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	Therapeutic Drug Monitoring - TDM. ARUP Consult^©. Retrieved October 15, 2018, from: https://arupconsult.com/content/therapeutic-drug-monitoring

Therapeutic Drug Monitoring - TDM

Quick Answers

What is the purpose of therapeutic drug monitoring (TDM)?

When should TDM testing be performed?

What specimens are appropriate for TDM?

How should results be interpreted?

Indications for Testing

Specimen Selection

Serum/Plasma and Whole Blood

Whole Blood

Oral Fluid (Saliva)

Urine

Timing of Specimen Collection

Commonly Used Testing Strategy

Frequently Asked Questions

ARUP Lab Tests

Antibiotic Tests

Anticonvulsant/Antiepileptic Tests

Antidepressant Tests

Antifungal Tests

Antipsychotic Tests

Cardiovascular Drug Tests

Immunosuppressant Tests

Nonopioid Pain Medication Tests

Oncology Tests

Opiate/Opioid Analgesic Tests

Sedative-Hypnotics Tests

Medical Reviewers

References

Additional Resources

References from the ARUP Institute for Clinical and Experimental Pathology®

References from the ARUP Institute for Clinical and Experimental Pathology^®