Paper Analytical Devices for Fast Field Screening of Beta Lactam Antibiotics and Antituberculosis Pharmaceuticals

Abstract

Reports of low quality pharmaceuticals have been on the rise in the last decade with the greatest prevalence of substandard medicines in developing countries, where lapses in manufacturing quality control or breaches in the supply chain allow substandard medicines to reach the marketplace. Here, we describe inexpensive test cards for fast field screening of pharmaceutical dosage forms containing beta lactam antibiotics or combinations of the four first-line antituberculosis (TB) drugs. The devices detect the active pharmaceutical ingredients (APIs) ampicillin, amoxicillin, rifampicin, isoniazid, ethambutol, and pyrazinamide, and also screen for substitute pharmaceuticals such as acetaminophen and chloroquine that may be found in counterfeit pharmaceuticals. The tests can detect binders and fillers like chalk, talc, and starch not revealed by traditional chromatographic methods. These paper devices contain twelve lanes, separated by hydrophobic barriers, with different reagents deposited in the lanes. The user rubs some of the solid pharmaceutical across the lanes and dips the edge of the paper into water. As water climbs up the lanes by capillary action, it triggers a library of different chemical tests and a timer to indicate when the tests are completed. The reactions in each lane generate colors to form a “color bar code” which can be analyzed visually by comparison to standard outcomes. While quantification of the APIs is poor compared to conventional analytical methods, the sensitivity and selectivity for the analytes is high enough to pick out suspicious formulations containing no API or a substitute API, as well as formulations containing APIs that have been “cut” with inactive ingredients.

Substandard/Counterfeit Antimicrobial Drugs

“…Substandard drugs can be detected by different methods, including inspection, colorimetric methods, chromatography, and spectrometry (Table 3) (9,12,31,43,45,(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106). A three-level approach (107) consisting of different quality control procedures has been proposed to detect substandard/counterfeit antimicrobials.…”

Field-Deployable Raman Anti-Counterfeit Screening of Tamiflu Capsules

“…Acetaminophen, the active ingredient in Tylenol, has been reported as a commonly incorporated cheaper substitute present in counterfeits because of its ability to reduce fever and pain, leading the patient to believe that the medicine is producing a therapeutic effect [13]. Acetaminophen and other common, relatively inexpensive inactive ingredients were used to make the simulated counterfeits in this study.…”

Paper and Fiber-Based Bio-Diagnostic Platforms: Current Challenges and Future Needs

“…One approach to perform equipment-free analysis relies upon color intensity comparators using an external calibration or standard calibration integrated within the device [143,144]. Weaver et al reported a cost-effective "color barcode" test for the rapid screening and quality control of pharmaceutical drugs [145]. The fabricated device was divided into twelve individual lanes, on which the solid pharmaceutical product was mounted and the edge dipped into the chosen media.…”

“…Each lane specifically reacted to one type of analyte (e.g., ampicillin, amoxicillin, and rifampicin) and a corresponding colored lane, visually compared with the reference was indicative of a "positive I.D." [145]. Another interesting study by Zhu et al reported a self-calibrating sensor for glucose measurement.…”