Henderson-Hasselbalch and Ionisation Chart

pH decides how much of a drug is ionised. The unionised form crosses membranes; the ionised form is trapped.

Inputs

Worked example

Loads a hand-worked test case from the spec, then shows the expected answer.

The drug

pKa
pH: 7.4 — drag to explore, or type a value below.
pH

Try a real drug

Urine pH ranges from 5.0 to 8.0.

Percent ionised against pH

Percent ionised

— % ionised

Percent ionised at the chosen pH. The rest is unionised, and that is the form that crosses membranes.

Weak acid: % ionised = 100 / (1 + 10^(pKa − pH))  ·  Weak base: % ionised = 100 / (1 + 10^(pH − pKa))
At pH = pKa, exactly half is ionised. One pH unit away, the ratio is 10 to 1.

Checked against five hand-worked examples (see the page source comments).

Results are shown to 2 decimal places.

Ionised against unionised at the chosen pH.

Set the pKa and the pH, then tap Show ionised percent.

Ionisation at body pH values
PlacepH% ionised% unionised
Stomach1.5——
Duodenum6.0——
Blood7.4——
Urine5.0–8.0——

For learning only. Not for patient care decisions. Always check with a qualified professional and the product label.

This is the pH-partition idea: real absorption also depends on transporters, surface area and solubility.

How it works

A weak acid or base is not one thing: it is a mixture of an ionised form and a unionised form, and pH sets the balance. The Henderson-Hasselbalch equation gives the ratio: for a weak acid, pH = pKa + log([A−]/[HA]); for a weak base, pH = pKa + log([B]/[BH+]). When pH equals pKa, the two forms are equal, half and half. One pH unit away, the ratio is 10 to 1. Two units away, it is 100 to 1.

That matters because only the unionised form is fat-soluble enough to cross a cell membrane. Aspirin is a weak acid with pKa 3.5. In the stomach at pH 1.5, only about 0.99% is ionised, so about 99% is unionised and it is absorbed well there. In blood at pH 7.4, about 99.99% is ionised, so it is trapped in the blood and cannot slip back across membranes easily. A weak base does the opposite: morphine, pKa 8.0, is about 80% ionised at blood pH 7.4, and almost fully ionised in the stomach, so it is poorly absorbed there and better absorbed further down the gut where the pH is higher.

The same idea explains ion trapping. Make the urine alkaline and a weak acid becomes more ionised there, so it cannot be reabsorbed and leaves the body faster. That is why sodium bicarbonate is used in aspirin overdose. The curve shows the whole story at a glance: it bends at the pKa, and the steep part is where a small pH change makes a big difference.