Date Published: January 6, 2018
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): Hui Pan, William Ba-Thein.
Global Pharma Health Fund (GPHF) Minilab™, a semi-quantitative thin-layer chromatography (TLC)–based commercially available test kit, is widely used in drug quality surveillance globally, but its diagnostic accuracy is unclear. We investigated the diagnostic accuracy of Minilab system for antimicrobials, using high-performance liquid chromatography (HPLC) as reference standard. Following the Minilab protocols and the Pharmacopoeia of the People’s Republic of China protocols, Minilab-TLC and HPLC were used to test five common antimicrobials (506 batches) for relative concentration of active pharmaceutical ingredients. The prevalence of poor-quality antimicrobials determined, respectively, by Minilab TLC and HPLC was amoxicillin (0% versus 14.9%), azithromycin (0% versus 17.4%), cefuroxime axetil (14.3% versus 0%), levofloxacin (0% versus 3.0%), and metronidazole (0% versus 38.0%). The Minilab TLC had false-positive and false-negative detection rates of 2.6% (13/506) and 15.2% (77/506) accordingly, resulting in the following test characteristics: sensitivity 0%, specificity 97.0%, positive predictive value 0, negative predictive value 0.8, positive likelihood ratio 0, negative likelihood ratio 1.0, diagnostic odds ratio 0, and adjusted diagnostic odds ratio 0.2. This study demonstrates unsatisfying diagnostic accuracy of Minilab system in screening poor-quality antimicrobials of common use. Using Minilab as a stand-alone system for monitoring drug quality should be reconsidered.
Poor-quality drugs are a serious public health problem worldwide. According to the World Health Organization (WHO),1 poor quality drugs include substandard antimicrobials, which are authorized medical products failing to meet either their quality standards and/or specifications, and falsified antimicrobials, which deliberately/fraudulently misrepresent their identity, composition, or source. The prevalence of poor-quality antimicrobials varies from 0% to more than 50% globally, and their consequences as treatment failure, drug resistance, adverse drug events, and even death have been frequently reported.2
The STARD flowchart of the study is shown in Figure 1. Five kinds of antimicrobials in 506 batches were purchased from community pharmacies in Shantou, Guangdong, China, in this cross-sectional study (May to July 2013) as described previously.3 The selection criteria3 for these antimicrobials were as follows: 1) frequently used in hospitals and pharmacies17; 2) easily destroyed under suboptimal storage conditions2,17; 3) commonly reported to have no active ingredient2,17; 4) listed in the National Essential Drug List of China.3,17
Our results are summarized in Tables 1 and 2. Of 506 batches of antimicrobial samples, 2.6% (13/506) did not meet the standard limits of the Minilab TLC system, but all of them (13/13) were within the expected quality standards of the PPRC in the HPLC system. This false positive detection occurred exclusively with cefuroxime axetil, accounting for 14.3% of cefuroxime axetil samples (13/91). On the other hand, false negativity was seen in 15.2% of samples (77/506) that met the quality standard limits in the Minilab TLC but failed in the HPLC system. Twenty-two percent (17/77) of the poor-quality samples were higher than the upper standard limit of the PPRC. Accordingly, the characteristics of Minilab TLC test were recorded as follows: Sn 0% (95% CI: 0– 4.7%); Sp 97.0% (95% CI: 94.9–98.4%); PPV 0; NPV 0.8 (95% CI: 0.8–0.9); PLR 0; NLR 1.0 (95% CI: 1.0–1.0); DOR 0; and ADOR 0.2 (95% CI: 0.01–3.4).
The prevalence of poor-quality antimicrobials as determined by the Minilab system varies by country and by drug from 0% to 26%.9–13,27,28 For example, the prevalence of poor-quality amoxicillin was between 0% and 10% in Tanzania, Ghana, Nigeria, and the United Kingdom.13,27