title: Dose-to-dose variations with single packages of counterfeit medicines and adulterated dietary supplements as a potential source of false negatives and inaccurate health risk assessments.
abstract: In this report, we show three examples of how the variability in dose units in single packages of counterfeit medicines and adulterated dietary supplements may contribute to a false negative screening result and inaccurate health risk assessments. We describe a counterfeit Viagra 100mg blister pack and a box of an instant coffee both containing dose units with and without an active pharmaceutical ingredient (API). We also describe a purportedly herbal slimming product with capsules that mutually differed in API and impurities. The adulterated dietary supplements contained sibutramine, benzyl-sibutramine, N-desmethyl-sibutramine (DMS), N,N-didesmethyl-sibutramine (DDMS) and several other related impurities. Counterfeit medicines and adulterated dietary supplements are a health risk because their quality is unreliable. Health risks are even greater when such unreliability extends to fundamental differences between dose units in one package. Because dose-to-dose variability for these products is unpredictable, the confidence interval of a sample size is unknown. Consequently, the analyses of a selection of dose units may not be representative for the package. In the worst case, counterfeit or unauthorised medicines are not recognised as such or a health risk is not identified. In order to reduce erroneous results particular care should be taken when analysing a composite of dose units, when finding no API in a dietary supplement and when finding conformity in a suspect counterfeit medicine.
authors.affiliation: National Institute for Public Health and the Environment, Postbox 1, 3721MA, Bilthoven, The Netherlands. Electronic address: bastiaan.venhuis@rivm.nl.
authors.forename: B J
authors.initials: BJ
authors.lastname: Venhuis
authors.affiliation: Dutch Customs Laboratory, Postbox 58933, 1040ED, Amsterdam, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Zwaagstra
authors.affiliation: National Institute for Public Health and the Environment, Postbox 1, 3721MA, Bilthoven, The Netherlands.
authors.forename: P H J
authors.initials: PH
authors.lastname: Keizers
authors.affiliation: National Institute for Public Health and the Environment, Postbox 1, 3721MA, Bilthoven, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: de Kaste
mesh_terms: D003069:Coffee / Q000737:chemistry; D058110:Counterfeit Drugs / Q000737:chemistry*; D019587:Dietary Supplements / Q000032:analysis*; D004340:Drug Contamination; D005188:False Negative Reactions; D010879:Piperazines / Q000737:chemistry; D011687:Purines / Q000737:chemistry; D012306:Risk; D018570:Risk Assessment / Q000379:methods; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000737:chemistry
chemical_list: D003069:Coffee; D058110:Counterfeit Drugs; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
keywords: Benzyl-sibutramine; Counterfeit medicines and adulterated dietary supplements; Dose-to-dose variability; Sibutramine analogues; UPLC-QTOF-MS/MS