How much palladium is in ibuprofen and is it harmful?

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Category: Pharmaceuticals and Fine Chemicals

Subject: How much palladium is in ibuprofen and is it harmful?



I heard that there is palladium in ibuprofen tablets so how much is present and are the tablets safe?


Ibuprofen or 2-(4-isobutylphenyl) propionic acid is a common over-the-counter pain medication available in many countries. Its synthesis involves a palladium catalyst, which is used to form the carboxylic acid group in the final step via a hydrocarboxylation reaction using carbon monoxide (1–3).

Because the palladium is introduced in the last step of the synthesis, its removal is a particularly important challenge because there are no further steps or cleanup which might remove the metal.

The amount of palladium, like other metals that are not intended to be part of the active ingredients, that is allowed to remain in pharmaceutical products such as ibuprofen tablets is specified by regulatory bodies. For example, the European Union, Switzerland, Japan, USA and Canada follow the recommendations of ICH Expert Working Group, which classifies palladium as “a route dependent human toxicant”. The Q3D classification calculates a safe limit based on the evidence available to date, which includes data in scientific journals, government reports, regulatory standards and regulatory authority research (4).

Manufacturers must therefore ensure that any traces of palladium catalyst in the final product are removed to below the required levels.

This can be done in a number of ways including the use of a scavenger (which can be added to the reaction mixture or used in a column through which the product stream is sent). The scavenger selectively picks up the palladium leaving the active ingredient clean (5).

It is worth noting that palladium in metal form, including jewellery and medical implants, is generally considered biocompatible and harmless to the human body (6).

 Answered on 14th September 2016


1. E. J. Jang, K. H. Lee, J. S. Lee and Y. G. Kim, J. Mol. Catal. A: Chem., 1999, 138, (1), 25 LINK

2. V. Elango, K. G. Davenport, M. A. Murphy, G. N. Mott, E. G. Zey, B. L. Smith and G. L. Moss, Hoechst Celanese Corp, European Patent Appl. 0,400,892; 1990

3. For a more accessible guide to ibuprofen synthesis see: The Royal Society of Chemistry, Chemistry in your Cupboard, Nurofen:

4. “ICH Harmonised Guideline, Guideline for Elemental Impurities, Q3D”, Current Step 4 Version, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, 16th December, 2014 LINK

5. S. Phillips and P. Kauppinen, Platinum Metals Rev., 2010, 54, (1), 69 LINK

6. B. Woodward, Platinum Metals Rev., 2012, 56, (3), 213 LINK



Answered by: Sara Coles

Affiliation: Johnson Matthey Technology Review