Therapeutic drug monitoring, or TDM, is the practice of measuring drug concentrations in blood to keep dosing inside the therapeutic range. The therapeutic range is the concentration window where a drug is effective without being toxic. For most medications, the body handles a wide margin of safety and TDM is unnecessary. For a small but clinically important group of drugs, that margin is razor thin. Those drugs have what is called a narrow therapeutic index. A little too low and the drug does nothing. A little too high and the patient ends up in renal failure or with hearing loss or a cardiac arrhythmia.
That is where the phlebotomist comes in. The lab can run an assay accurate to the nanogram, but if the sample was drawn at the wrong time, the result is meaningless. Worse, it can be actively misleading. A vancomycin drawn an hour after the dose looks like a peak, not a trough, and a provider who acts on it might cut the dose on a patient who actually needs more drug. TDM lives or dies by timing, and timing is what you control.
Why Timing Is the Whole Game
A drug level is not a static number. After a dose is administered, the concentration in blood rises as the drug is absorbed and distributed, peaks at some predictable point, then falls as the liver metabolizes it and the kidneys excrete it. By the time the next dose is due, the level has dropped to its lowest point. The whole curve is in motion every single hour.
If the lab gets a sample without knowing where on that curve it was collected, the number is just a number. There is no way to interpret it. The provider needs to know whether they are looking at the highest concentration the patient saw or the lowest one. That distinction tells them whether the drug is exceeding the toxic threshold or dropping below the effective minimum. Get the timing wrong and the result tells the wrong story.
This is why every TDM lab requisition asks for two times: time of last dose and time of draw. Sometimes a third, the route of administration. The lab uses those values to interpret the result. Without them, many labs will reject the sample outright.
Peak vs Trough
The two main TDM draws are the peak and the trough. They answer different questions and they are drawn at different times.
Trough levels are drawn just before the next scheduled dose, typically within 30 minutes prior. The trough represents the lowest concentration the drug reaches between doses. It tells the provider whether the drug is staying above the minimum effective concentration during the interval. If the trough is too low, the patient is going untreated for part of every dosing cycle. If the trough is too high, the drug is accumulating and toxicity is coming.
Trough is the more commonly ordered level for most TDM drugs because it is easier to time. The patient sees the next scheduled dose on the medication record, and you draw 30 minutes before that. Simple.
Peak levels are drawn at a specified time after the dose is given. The exact timing depends on the drug, the route, and the formulation. For an IV infusion, the peak is usually drawn 30 minutes after the infusion ends. For an oral drug, peak might be 1 to 2 hours after the dose. For an intramuscular injection, somewhere in between. The peak represents the highest concentration the drug reaches and tells the provider whether the patient is hitting the toxic threshold.
Peaks are harder to time correctly because they depend on knowing exactly when the dose was completed, not just when it was hung. An IV bag that runs slow, or a nurse who hangs the bag late, throws the peak window off.
Quick Reference: Common TDM Drugs
| Drug | Typical Draw | Timing |
|---|---|---|
| Vancomycin | Trough | 30 minutes before next dose |
| Gentamicin / Tobramycin / Amikacin | Peak and trough | Trough before dose; peak 30 minutes after IV ends |
| Digoxin | Trough | At least 6 to 8 hours after dose, typically morning of next dose |
| Phenytoin | Trough | Just before next dose |
| Lithium | Trough | 12 hours after last dose, before morning dose |
| Theophylline | Trough or steady-state | Just before next dose |
| Valproic acid | Trough | Just before next dose |
| Cyclosporine | Trough | Just before next dose |
The pattern is clear. Most TDM is trough monitoring. Aminoglycosides are the main exception where peaks matter, because the toxic effects (nephrotoxicity and ototoxicity) correlate with peak levels and the bactericidal effect requires hitting a high peak to be effective.
Steady State
One concept that ties all of this together is steady state. When a patient starts a new drug, the first few doses do not produce stable levels. The drug is still accumulating with each dose. After enough doses, input equals output and the concentrations cycle predictably between the same peak and the same trough every interval. That is steady state.
The rule of thumb is that steady state is reached after 4 to 5 half-lives of the drug. For vancomycin with a half-life around 6 hours in healthy kidneys, that means 24 to 30 hours, or roughly the fourth dose on a typical q12h schedule. For digoxin with a half-life of 36 hours, steady state takes about a week.
TDM levels drawn before steady state are usually not interpretable for dose adjustment. They reflect a system still in flux. Most TDM protocols specifically order the level around the third or fourth dose so the result reflects steady state. The phlebotomist will see this on the requisition as something like "draw before 4th dose" or simply "trough at steady state."
An exception is vancomycin in critical illness, where some protocols order an early level after the loading dose to check if the patient hit therapeutic concentrations quickly enough. That is not a steady-state level and the provider knows that. The phlebotomist still draws when the requisition says to draw.
Documentation Requirements
Every TDM draw needs three pieces of information documented on the lab requisition or in the LIS:
- Time of last dose. Get this from the medication administration record (MAR) or directly from the nurse. Do not guess. If the MAR says 0800 and the nurse confirms the dose finished at 0815, document 0815. The 15 minutes can matter for a peak level.
- Time of draw. The exact time the sample was collected, not the time it was ordered or the time you walked into the room.
- Route of administration. IV, IM, oral, subcutaneous. The pharmacokinetics differ. An oral dose peaks later than an IV dose.
Some facilities also require you to note whether the patient is at steady state, which dose number this is, and any concurrent medications that affect drug levels. Check your facility protocol.
If any of this information is missing or unclear, stop and verify before you draw. A correctly timed sample with the wrong documented time is worse than no sample at all, because the lab will run it and the provider will act on a result that does not mean what they think it means.
The Big Errors That Waste Samples
TDM has its own catalog of preanalytical errors. These are the ones that show up most often and the ones the NHA CPT likes to test.
Drawing through the IV line the drug is being given through. This is the worst. If a patient has a vancomycin drip running through a central line and you draw your trough out of that same lumen, you are drawing diluted vancomycin from the line itself. The result will be massively elevated and completely wrong. The basic rule: never draw a TDM level from the line that is delivering the drug. If a multi-lumen line is in use and the drug is on a separate lumen, some facilities allow draws from a different lumen with proper waste volume, but the safest practice is a peripheral stick from the opposite arm.
Drawing too early or too late. A trough drawn an hour before it was supposed to be drawn is not a trough. The level is still falling and has not bottomed out. A peak drawn too early misses the true peak, drawn too late misses it on the way down. The window matters. For vancomycin trough, 30 minutes before the dose is the standard. Drawing 90 minutes before will give a falsely elevated trough and the provider may decrease a dose that did not need decreasing.
Not documenting time of last dose. A trough sample arrives in the lab with a draw time but no dose time. The lab cannot calculate the interval. The result gets reported but flagged as uninterpretable, or it gets cancelled outright. Either way, the patient gets stuck again and an extra hour passes before the dose adjustment.
Drawing during the loading dose phase rather than at steady state. Some patients get a loading dose, often a higher one-time dose to bring concentrations up quickly. Drawing a trough between the loading dose and the first maintenance dose gives a number that does not reflect the maintenance regimen. The lab requisition should specify which dose to draw before. If it just says "vanc trough" and you can see on the MAR that the patient is still in the loading phase, that is worth a phone call to the floor before you stick.
Drawing the wrong type of sample. Most TDM drugs are run on serum (red top or SST). Some, like cyclosporine, are run on whole blood EDTA (lavender top). Drawing a serum sample for a cyclosporine level produces nothing usable. Check the lab manual or the requisition before you collect.
What the Phlebotomist Actually Does
The role on a TDM draw is fairly defined. Read the requisition carefully. Confirm the timing matches what the order says. Verify with the nurse if anything is unclear, especially the time of last dose if the MAR is ambiguous. Draw at the requested time, not earlier and not later. Document the draw time, the dose time, and the route on the requisition or in the LIS. Label the tubes correctly. Get the sample to the lab promptly, since some TDM drugs (especially aminoglycosides) are time-sensitive after collection.
If you cannot draw at the requested time, do not just shift the draw and pretend it was on time. Document the actual draw time and notify the lab. The interpretation may still be possible with adjusted calculations, or the level may need to be redrawn. That call belongs to the lab and the provider, not to you. Your job is accurate documentation.
Practice Scenarios
Question 1: A nurse calls the lab to request a phlebotomist for a vancomycin trough. The next dose is scheduled for 0800. What is the correct draw time and how should it be documented?
Show Answer
Answer: Draw the sample at approximately 0730, within 30 minutes before the 0800 dose. Document the actual time of draw, the time of the previous dose (typically 12 hours earlier at 2000), and the route of administration (IV). Vancomycin troughs are drawn just before the next scheduled dose to capture the lowest concentration in the dosing interval.
Question 2: A phlebotomist is asked to collect a peak and trough for gentamicin. The IV infusion ends at 1000 and the next dose is scheduled for 1800. When should the peak and trough be drawn?
Show Answer
Answer: The peak should be drawn at 1030, which is 30 minutes after the IV infusion ends. The trough should be drawn at approximately 1730, within 30 minutes before the next scheduled dose at 1800. Aminoglycosides like gentamicin require both peak and trough monitoring because the bactericidal effect depends on hitting a sufficient peak while toxicity correlates with elevated trough levels.
Question 3: A phlebotomist arrives to draw a vancomycin trough on a patient with a triple-lumen central line. The vancomycin is infusing on the distal lumen. What is the safest collection approach?
Show Answer
Answer: Perform a peripheral venipuncture on the opposite arm. Drawing from the same lumen as the infusing drug will produce a falsely elevated result that is clinically meaningless. Even drawing from a different lumen on the same central line carries contamination risk and many facility protocols require a peripheral stick for accurate TDM samples. When in doubt, the peripheral draw is the safest path.
Bottom Line for the Exam
TDM is timing. The lab assay is the easy part. The hard part is making sure the sample reflects the right point on the concentration curve and that the lab knows where on the curve it was drawn. Trough before next dose. Peak at the specified interval after the dose. Document the dose time, the draw time, and the route. Never draw through the line delivering the drug. When the timing on the requisition is ambiguous, stop and verify before sticking. A few minutes spent getting it right saves the patient a redraw and the provider a wrong decision.