Figure 1 – The sample is applied to the PAD.Do you ever wonder if the drug you’re considering buying is what it says it is or if it is still potent? These concerns were addressed in a report by Marya Lieberman (University of Notre Dame, South Bend, Ind.) at the recent American Chemical Society Meeting. Paper analytical devices (PADs) are rectangular, cell-phone-sized test cards that have 12 lanes separated by wax walls. Each lane is printed with a color-generating reagent that reacts to specific functional groups of the active pharmaceutical ingredient (API) and excipients.
The device works by examining the reference pattern in the assay packaging to confirm drug composition, and the color intensity provides a semiquantitative assay. A PAD designed for the antibiotic ceftriaxone was used to monitor temperature-induced degradation as part of a stability study. Results were compared and validated with LC/MS, which was run in parallel.
Figure 2 – The PAD is run by dipping the bottom of the card in water. Shown is pharmacist Mercy Maina.The workflow (see Figures 1–3) was as follows. A ceftriaxone pill was crushed to a powder and rubbed across the device’s 12 lanes. The card was placed into a shallow pool of water, where it was absorbed, revealing some of the pill’s components along the bands of the printed reagents. This reaction produced a pattern of colored spots that provide qualitative identification of the components. The pattern can be compared to that generated by an authentic reference product. These researchers used the PAD to assay ceftriaxone products in Kenya, which was chosen for its climate: ceftriaxone degrades rapidly if the storage temperature is too high. In addition, counterfeit drugs are a serious problem in Kenya.
PAD technology is reminiscent of colorimetric reagents that were once popular in thin-layer chromatography, some of which produced beautiful colors and were very specific. Infrared spectrometry and melting points of reaction products were all we had. Today, NMR, MS, IR and even X-ray crystallography, with or without a synchrotron light source, provide much more definitive information—but at a price. Domain-specific knowledge is needed to operate the instruments and interpret the output.
Figure 3 – The user examines the “color bar code” formed at the top of the card.Since colorimetric reactions in the PAD are functional-group or perhaps compound-specific, each assay will probably need to be engineered and validated. With a cost of less than a dollar for each test, however, the device should be affordable in resource-limited situations.
While Dr. Lieberman is primarily interested in providing low-cost assays suitable for less-developed countries, it is easy to see how the PAD could eventually be used to confirm product authenticity (for example, in meats, fish, etc.) as well as help nutraceutical vendors demonstrate that contents agree with container labels. Law enforcement might be interested too, especially since some of the preliminary tests used in the field, such as Scott’s test for cocaine, lack specificity.