Percentage ionisation

Calculate what fraction of a weak acid or weak base is ionised at a given pH, with an interactive curve showing how it changes across the physiological range.

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What is this for?

Only the un-ionised form of a drug crosses lipid membranes readily. The proportion ionised at any pH is fixed by the pKa, and this single relationship explains gastric versus intestinal absorption, ion trapping in the renal tubule, and why urine alkalinisation accelerates salicylate elimination.

How to use it

Select whether the drug is a weak acid or a weak base. This determines the sign of the exponent and reverses the shape of the curve.
Enter the pKa and the pH of the compartment you are interested in.
Use the curve and the site table to see how the ionisation changes across the gastrointestinal tract and the renal tubule.

Worked example

A weak acid has a pKa of 3.5. What percentage is ionised in plasma at pH 7.4?

Answer: 100 ÷ (1 + 10^(3.5 − 7.4)) = 100 ÷ (1 + 10^−3.9) = 100 ÷ 1.000126 = 99.99% ionised. Almost none is available to cross membranes at plasma pH.

Clinical pearls & pitfalls

At pH equal to pKa, exactly 50% is ionised for both acids and bases. This is the anchor point for every mental estimate — work outward from there in ten-fold steps per pH unit.
Weak acids are more un-ionised in acid and weak bases more un-ionised in base. The mnemonic "like stays un-ionised in like" captures it: acids stay un-ionised in acidic environments.
Ion trapping is the clinical consequence. Alkalinising the urine with sodium bicarbonate ionises salicylate in the tubule, preventing reabsorption and accelerating elimination — a standard part of salicylate overdose management.
This also explains why most weak acids are absorbed largely in the small intestine despite being un-ionised in the stomach: surface area and transit time overwhelm the ionisation advantage.
A drug that is 99.99% ionised is not entirely impermeable. The remaining 0.01% is continuously replenished as it crosses, so absorption still occurs, just slowly.

Assumptions & limitations

Predicts the ionisation equilibrium only. Actual absorption also depends on surface area, transit time, blood flow, active transport, and efflux pumps such as P-glycoprotein.
Assumes a single ionisable group. Amphoteric and polyprotic drugs need a species-specific treatment at each pKa.
Uses concentrations rather than activities and ignores ionic strength and temperature effects on pKa.
The pH-partition hypothesis it embodies is a simplification that fails for drugs absorbed by carrier-mediated transport.

References

Sinko PJ. Martin's Physical Pharmacy and Pharmaceutical Sciences. 7th ed. Wolters Kluwer.
Shore PA, Brodie BB, Hogben CA. The gastric secretion of drugs: a pH partition hypothesis. J Pharmacol Exp Ther. 1957;119(3):361-369.
Chyka PA, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol. 2007;45(2):95-131.