Residual active pharmaceutical ingredient on the primary packaging of medicines: A valuable GMP-marker

Medicines are meant to help people and treat their conditions and to promote general well-being of all members of the society. Unfortunately, this is being compromised by the distribution and sale of poor-quality medicines around the world, being a consequence of non-GMP manufacturing. In this study, the contamination of the outer primary packaging with active pharmaceutical ingredient (API, i.e. artemether) is investigated as a possible and objective, quantifiable marker for GMP-compliance. First, an analytical UPLC-MS method was developed and verified for artemether, with emphasis on the quantification in the lower concentration range. Second, a swabbing procedure for the outer surface of plastic bottles (powders for suspension) was developed, including a swabbing recovery of the API from the bottle surfaces. Finally, twenty antimalarial samples were investigated. All of them showed some degree of outer contamination; however, large differences in the amount of API contamination between the different samples was observed, ranging between 4 and 144 ng/cm². A positive correlation was found between the amount of artemether on the packaging and the number of information elements missing on the packaging or leaflet, which was used as one of the tools to evaluate the GMP status of the manufacturer.