Abstract

Beta lactam antibiotics make up a significant fraction of the anti-infective market, but there are many poor quality products that cause bad clinical outcomes and contribute to development of resistant pathogens. Underdosing can result from degradation, sloppy or negligent manufacturing, or outright falsification. In response to the unacceptable levels of substandard beta lactam antibiotics found in our 2013-2015 sample pool in Kenya, we developed an inexpensive paper analytical device, or PAD, to detect beta lactam antibiotic pills that contain less than 90% of the stated API. A sample of the antibiotic undergoes base hydrolysis to form free thiol groups, which are then oxidized with excess iodine. The remaining iodine is back-titrated on the PAD by thiosulfate. The test takes about 30 minutes and can be done in a laboratory equipped with a centigram balance. The accuracy and precision of the paper test card assay were measured for ampicillin and amoxycillin tablets, and the results were compared with an HPLC assay. The quantitative accuracy for the PAD was 4-5% with intermediate precision between three analysts of 2%.  The paper cards correctly categorized 85-90% of a representative sample pool of good and bad quality antibiotics (n = 80 for amoxicillin, n = 56 for ampicillin).   The PAD could be used as a quick screening method for monitoring post-market antibiotic quality.  I will discuss some of the opportunities and problems that arose as we tried to take this technology out of the lab and into the world.