Medical Experts
Johnson-Davis
McMillin
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 confirm concentrations are neither subtherapeutic nor potentially toxic. The purpose of TDM is to optimize dosing to target a therapeutic plasma drug concentration while minimizing toxicity. TDM is often influenced by pharmacogenetics (PGx) factors. Refer to the ARUP Consult Germline Pharmacogenetics - PGx topic for detailed information about PGx testing and recommendations.
Quick Answers for Clinicians
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. Therapeutic drug monitoring (TDM) allows for personalization of drug selection and dose, evaluation of adherence, and investigation of changes in pharmacokinetics (eg, drug-drug interactions). In many cases, germline pharmacogenetics (PGx) testing can inform TDM testing.
Therapeutic drug monitoring (TDM) should be performed when the patient has achieved steady-state concentration, has changed drug therapy, or has had a change in response to treatment (eg, toxicity).
Whole blood, serum, and plasma specimens can be used to assess whether the drug dosage achieved the targeted therapeutic range and to evaluate patient adherence. Urine drug and metabolite concentrations do not correlate with signs and symptoms of drug therapy or toxicity and should not be used for therapeutic drug monitoring (TDM).
Test 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 (PGx), ie, whether they demonstrate 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 with a:
- 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)
- Potential for severe adverse effects (dose related)
TDM is also used to identify drug-drug or food-drug interactions and to monitor patient compliance with treatment, status during decontamination or detoxification, and changes in drug concentrations related to aging, pregnancy, or clinical status. A list of example drug-drug interactions that may be identified by TDM can be found on the U.S. Food and Drug Administration’s Drug Development and Drug Interactions web page.
TDM should be performed once a drug has reached steady-state concentration.
Specimen Selection
Therapeutic and toxic ranges are typically established for serum, plasma, and whole blood specimens. Urine should not be utilized for TDM.
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, and whole blood specimens are also appropriate for patients on dialysis, for suspected cases of malabsorption (eg, due to gastric bypass), and for 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 red blood cells (RBCs).
Oral Fluid (Saliva)
Oral fluid drug concentrations tend to correlate with serum/plasma concentrations. The window of drug detection is approximately 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 is not a recommended specimen type 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 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 concentrations (0-60 minutes before dose administration)
- Peak concentrations (generally 1-2 hours after drug administration; however, this is highly drug dependent)
- Random concentrations
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 an individual has consistently received 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, solubility, stability)
- Patient age
- Patient body composition and sex
- Patient pathophysiology and pharmacokinetics
- Coadministration of other medications
- Hydration and nutrition status
- Analytic 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 Laboratory Tests
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 0.5-2 µg/mL
Toxic level: >3 µg/mL
Quantitative Immunoassay
Immunoassay
Therapeutic range: 0.8-2 ng/mL
Toxic level: >2.4 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 0.2-1 µg/mL
Toxic level: >1.5 µg/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 0.5-2 µg/mL
Toxic level: >2 µg/mL
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
Note that therapeutic ranges depend on pathogen being treated.
Immunoassay
Trough levels:
- Optimal range: 4-8 µg/mL
- Toxic level: ≥8.1 µg/mL
Peak levels:
- Optimal range: 20-30 µg/mL
- Toxic level: ≥30.1 µg/mL
Immunoassay
Optimal range: 4-8 µg/mL
Toxic level: ≥8.1 µg/mL
Quantitative Bioassay
Normal peak serum concentration:
- 90-164 µg/mL with a 1 g intravenous (IV) dose
- 204-255 µg/mL with a 2 g IV dose
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
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
Quantitative Bioassay
Normal peak serum concentration:
- 7.7 µg/mL with a 1 g oral dose
- 7.6 µg/mL with a 1 g intramuscular (IM) dose
- 40 µg/mL with a 500 mg IV dose
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
Quantitative Bioassay
Normal peak serum concentration: 324 µg/mL with a 3.1 g IV dose of ticarcillin/clavulanate
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Peak serum concentration: 0.2-0.7 µg/mL approximately 2-3 weeks after a 250-500 mg dose of oral azithromycin
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography (HPLC)
Target range for conventional treatment of mycobacterial infections: 35-45 µg/mL approximately 1 hr after IM injection or 1 hr after the end of IV infusion
Target range for high-dose, three times weekly treatment of mycobacterial infection: 65-80 µg/mL approximately 1 hr after IM injection or 1 hr after the end of IV infusion
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Usual tuberculostatic (chronic) level: 2-5 µg/mL at 4 hrs after last dose
Toxic level: >10 µg/mL
Immunoassay
Optimal range: 5-10 µg/mL
Toxic level: >12 µg/mL
Immunoassay
Optimal range: 0.5-2 µg/mL
Toxic level: >2 µg/mL
Quantitative Spectrophotometry
Immunoassay
Optimal range: 30-40 µg/mL
Toxic level: ≥80.1 µg/mL
Fluorescence Polarization Immunoassay
Trough level (optimal): 10-20 µg/mL
Peak level (optimal): 30-40 µg/mL
Immunoassay
Optimal level: 10-20 µg/mL
Therapeutic range for significant infections: 15-20 µg/mL
Quantitative Electrochemiluminescent Immunoassay (ECLIA) with Acid Dissociation
Quantitative Electrochemiluminescence Immunoassay (ECLIA) with Acid Dissociation
Enzyme-Linked Immunosorbent Assay (ELISA)
Quantitative Liquid Chromatography-Tandem Mass Spectrometry /Electrochemiluminescent Immunoassay (ECLIA)
Qualitative Bridging Enzyme-Linked Immunosorbent Assay
Chromogenic Assay
Therapeutic range based on enoxaparin brand low-molecular-weight heparin
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 0.2-2 μg/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Carbamazepine-10,11 epoxide:
- Therapeutic range (proposed): 0.4-4 µg/mL
- Toxic level: >15 µg/mL
Total carbamazepine:
- Therapeutic range: 4-12 µg/mL
- Toxic level: >15 µg/mL
Quantitative Enzyme Multiplied Immunoassay Technique
Total carbamazepine:
- Therapeutic range: 4-12 µg/mL
- Toxic level: >15 µg/mL
Free carbamazepine:
- Therapeutic range: 1-3 µg/mL
- Toxic level: >3.8 µg/mL
Percent free carbamazepine: 8-35%
Immunoassay
Therapeutic range: 4-12 µg/mL
Toxic level: >15 µg/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Clobazam
Therapeutic range: 30-300 ng/mL
Toxic range: >500 ng/mL
N-Desmethylclobazam
Therapeutic range: 300-3,000 ng/mL
Toxic range: >5,000 ng/mL
Quantitative Enzyme Immunoassay
Therapeutic range: 40-100 µg/mL
Toxic level: >150 µg/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 30-60 μg/mL
Toxic level: ≥100 µg/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 2-20 µg/mL
Toxic level: not well established
Quantitative Enzyme Immunoassay
Therapeutic range: 10-40 µg/mL
Toxic level: not well established
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 1.0-10.0 µg/mL
Toxic level: ≥20 µg/mL
Quantitative Enzyme Immunoassay
Therapeutic range: 3-15.0 µg/mL
Toxic level: ≥20 μg/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 3-35 µg/mL
Toxic level: >40 µg/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Peak plasma concentration: ~460 ng/mL with daily administration of 6 mg at approximately 1.3 hrs after administration
Peak plasma concentration: ~800 ng/mL with single 12 mg dose
Enzyme Multiplied Immunoassay Technique (EMIT)
0-2 mos of age:
- Therapeutic range: 15-30 µg/mL
- Toxic level: ≥40.1 µg/mL
3 mos and older:
- Therapeutic range: 15-40 µg/mL
- Toxic level: ≥50.1 µg/mL
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Dose-related range (proposed): 2-10 µg/mL
Therapeutic range: not well established
Toxic level: not well established
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 3-30 µg/mL
Dose-related range (doses of 800-7,200 mg/day): 3-30 µg/mL
Toxic level: not well established
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Enzyme Immunoassay
Therapeutic range: 5-20 µg/mL
Toxic level: not well established
Fluorescence Polarization Immunoassay
Toxic level: ≥151 µg/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Enzyme Multiplied Immunoassay Technique
Therapeutic range: not well established
Toxic level: >80 µg/mL
Quantitative Enzyme Multiplied Immunoassay Technique
Total phenytoin:
- Therapeutic range: 10-20 µg/mL
- Toxic level: >30 µg/mL
Free phenytoin:
- Therapeutic range: 1-2.5 µg/mL
- Toxic level: >2.5 µg/mL
Percent free phenytoin: 8-14%
Quantitative Enzyme Multiplied Immunoassay Technique
Total valproic acid:
- Therapeutic range: 50-125 µg/mL
- Toxic level: >150 µg/mL
Free valproic acid:
- Therapeutic range: 7-23 µg/mL
- Toxic level: >30 µg/mL
Percent free valproic acid: 5-18%
Quantitative Enzyme Multiplied Immunoassay Technique
Therapeutic range: 1-2.5 µg/mL
Toxic level: >2.5 µg/mL
Enzyme Immunoassay
0-2 mos of age:
- Therapeutic range: 6-14 µg/mL
- Toxic level: ≥14.1 µg/mL
3 mos and older:
- Therapeutic range: 10-20 µg/mL
- Toxic level: ≥30.1 µg/mL
Immunoassay
Phenobarbital:
0-2 mos of age:
- Therapeutic range: 15-30 µg/mL
- Toxic level: ≥40.1 µg/mL
3 mos and older:
- Therapeutic range: 15-40 µg/mL
- Toxic level: ≥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.
Quantitative Gas Chromatography/Gas Chromatography-Mass Spectrometry (GC-MS)
Panel includes testing for amitriptyline (Elavil, Vanatrip), amoxapine, clomipramine (Anafranil), desipramine (Norpramin), desmethylclomipramine, desmethyldoxepin, desmethyltrimipramine, doxepin (Sinequan, Zonalon), fluoxetine, imipramine (Tofranil), maprotiline, mirtazapine, norfluoxetine, nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), trazodone, and trimipramine
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Drugs tested and therapeutic ranges/toxic levels:
- Amitriptyline (Elavil, Vanatrip): therapeutic range/toxic level not established
- Nortriptyline (Aventyl, Pamelor): therapeutic range, 50-150 ng/mL; toxic level, >500 ng/mL
- Total amitriptyline and nortriptyline: therapeutic range, 95-250 ng/mL; toxic level, >500 ng/mL
- Imipramine (Tofranil): therapeutic range/toxic level not established
- Desipramine (Norpramin): therapeutic range, 100-300 ng/mL; toxic level, >500 ng/mL
- Total imipramine and desipramine: therapeutic range, 150-300 ng/mL; toxic level, >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 level, >500 ng/mL
- Protriptyline (Vivactil): therapeutic range, 70-240 ng/mL; toxic level, >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 level, >900 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (total): 95-250 ng/mL
Toxic level: >500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Bupropion
- Therapeutic range: 10-100 ng/mL
- Toxic level: ≥400 ng/mL
Hydroxybupropion
- Therapeutic range: 850-1,500 ng/mL
- Toxic level: ≥2,000 ng/mL
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (total): 220-500 ng/mL
Toxic level: >900 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 100-300 ng/mL
Toxic level: >500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (total): 100-300 ng/mL
Toxic level: >500 ng/mL
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Gas Chromatography-Mass Spectrometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (total): 150-300 ng/mL
Toxic level: >500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 50-150 ng/mL
Toxic level: >500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 70-240 ng/mL
Toxic level: >400 ng/mL
Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 30-200 ng/mL
Toxic level: >300 ng/mL
Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 800-1600 ng/mL
Toxic level: not well established
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (venlafaxine and O-desmethylvenlafaxine): 195-400 ng/mL
Toxic level (venlafaxine and O-desmethylvenlafaxine): ≥800 ng/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 1-2 µg/mL
Metformin-related lactic acidosis is generally associated with plasma concentrations >5 µg/mL
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 5-20 µg/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic ranges:
- Itraconazole, localized infection: >0.5 µg/mL
- Itraconazole, systemic infection: >1.0 µg/mL
- Hydroxyitraconazole: no therapeutic range established
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: >0.7 µg/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (trough): 1-6 µg/mL
Toxic level: >6 µg/mL
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Peak plasma concentration: 20-340 ng/mL following oral administration of multiple doses of metoprolol tartrate (50-80 mg three times daily)
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 150-500 ng/mL
Toxic range: ≥1,000 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 30-300 ng/mL
Toxic level: ≥600 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: not well established
Toxic level: ≥1,500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 1.0-10.0 ng/mL
Toxic level: >15 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 5-20 ng/mL
Toxic level: >50 ng/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Mean Cmax values in serum:
Following single-dose administration of 40 mg: 54 ng/mL
Following single-dose administration of 80 mg: 64 ng/mL
Following steady-state administration of 40 mg: 48 ng/mL
Following steady-state administration of 80 mg: 79 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 20-80 ng/mL
Toxic level: ≥100 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 20-60 ng/mL
Toxic range: >120 ng/mL
Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range: 100-1,000 ng/mL
Toxic level: >1,000 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (risperidone): 20-60 ng/mL
Therapeutic range (9-hydroxyrisperidone [paliperidone]): 20-60 ng/mL
Toxic range: >120 ng/mL
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Colorimetry
Therapeutic range: 0.5-1.2 mmol/L
Toxic level: ≥1.6 mmol/L
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
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 level: >700 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Renal transplant (suggested target range): 800-1,700 ng/mL
Liver transplant (suggested target range): 600-1,000 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range:
- Kidney transplant (in combination with cyclosporine): 3-8 ng/mL
- Liver transplant (in combination with tacrolimus): 3-8 ng/mL
Toxic level: >15 ng/mL
Quantitative Immunoassay
Therapeutic range:
- Low dose: 0.5-1 µmol/L
- High dose/24 hrs: ≤5 µmol/L
- 48 hrs: ≤0.5 µmol/L
- 72 hrs: ≤0.1 µmol/L
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Mycophenolic acid:
- Therapeutic range: 1-3.5 µg/mL
- Toxic level: >25 µg/mL
Mycophenolic acid glucuronide:
- Therapeutic range: 35-100 µg/mL
- Toxic level: not well established
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range:
- Kidney transplant (in combination with cyclosporine): 4-12 ng/mL
- Liver transplant (proposed range): 12-20 ng/mL
Toxic level: >25 ng/mL
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 level: >25 ng/mL
Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (proposed): 50-100 µg/mL (>40 µg/mL associated with improved individual outcomes)
Toxic level: not well established
Quantitative Flow Cytometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
6-thioguanine (6-TG): >450 pmol/8 x 108 RBC associated with leukopenia
6-methylmercaptopurine (6-MMP): >5,700 pmol/8 x 108 RBC may be associated with hepatoxicity
Liquid Chromatography-Tandem Mass Spectrometry
Therapeutic range (proposed): 50-100 µg/mL (>40 µg/mL associated with improved individual outcomes)
Toxic level: not well established
Enzyme Immunoassay
Therapeutic range:
- 0-5 mos: 6-12 µg/mL
- 6 mos and older: 10-20 µg/mL
Toxic level:
- 0-5 mos: ≥20.1 µg/mL
- 6 mos and older: ≥25.1 µg/mL
The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Drug Testing topic.)
Spectrophotometry
Critical values:
- 4 hrs after ingestion: >150 µg/mL
- 12 hrs after ingestion: >40 µg/mL
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Spectrophotometry
Analgesic: 2-10 mg/dL
Anti-inflammatory: 10-30 mg/dL
Toxic level: ≥31 mg/dL
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
Quantitative Immunoassay
Low dose: 0.5-1 µmol/L
High dose:
- 24 hrs: ≤5 µmol/L
- 48 hrs: ≤0.5 µmol/L
- 72 hrs: ≤0.1 µmol/L
Quantitative Gas Chromatography
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
6-thioguanine (6-TG): >450 pmol/8 x 108 RBC associated with leukopenia
6-methylmercaptopurine (6-MMP): >5,700 pmol/8 x 108 RBC may be associated with hepatoxicity
The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Drug Testing topic.)
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Gas Chromatography-Mass Spectrometry
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Qualitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
(eg, for benzodiazepines, barbiturates, muscle relaxants)
The therapeutic range is based on serum predose (trough) draw at steady-state concentration.
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 level: >100 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
See individual drug analytes for therapeutic ranges and toxic thresholds
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Dose-related range (adult): 20-70 ng/mL (1-8 mg/d)
Toxic level: >80 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Dose-related range: 100-1,500 ng/mL (based on common dosages)
Toxic level: >2,500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Diazepam:
- Dose-related range: 200-1,000 ng/mL (based on normal dosages)
Nordiazepam:
- Dose-related range: 100-1,500 ng/mL (based on normal dosages)
- Toxic level: >2,500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Librium:
- Therapeutic range: 500-3,000 ng/mL (based on adult dose of 5-100 mg)
- Toxic level: >5,000 ng/mL
Nordiazepam:
- Therapeutic range: 100-1,500 ng/mL (based on normal dosages)
- Toxic level: >2,500 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Dose-related range: 50-240 ng/mL (based on adult dose of 1-10 mg/d)
Toxic level: >300 ng/mL
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Prazepam:
- Dose-related range: 20-60 mg/d
Nordiazepam:
- Dose-related range: 100-1,500 ng/mL
- Toxic level: >2,500 ng/mL
Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry
See individual drug analytes for therapeutic ranges and toxic thresholds
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
References
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FDA - Drug development and drug interactions
Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers. Last reviewed Mar 2020; accessed May 2022.
Refer to the Germline Pharmacogenetics topic for detailed information about PGx testing and recommendations related to the drug targets listed below.