Available online at www.sciencedirect.com Journal of Pharmaceutical and Biomedical Analysis 48 (2008) 303–309 An LC method for the simultaneous screening of some common counterfeit and sub-standard antibiotics Validation and uncertainty estimation M.C. Gaudiano ∗ , A. Di Maggio, E. Antoniella, L. Valvo, P. Bertocchi, L. Manna, M. Bartolomei, S. Alimonti, A.L. Rodomonte Dipartimento del Farmaco, Istituto Superiore di Sanit` a Viale Regina Elena, 299, 00161, Rome, Italy Received 12 October 2007; received in revised form 11 December 2007; accepted 17 December 2007 Available online 26 December 2007 Abstract Pharmaceutical counterfeiting is a worldwide public health problem, often under-recognised, especially in developing countries where th percentage of counterfeit and sub-standard medicines is dramatically high. Antibiotics, among the most widespread drug targeted by counterfeiters. World Health Organization emphasizes the need for development and distribution of screening methods explicit targeted to counterfeit drugs. In this paper is presented a single method for the simultaneous analysis of some of the mos essential antibiotics: ampicillin, amoxicillin + clavulanic acid, doxycycline, cloxacillin, chloramphenicol. A full validation w of linearity, precision, robustness and trueness; an assessment of uncertainty was carried out exploiting these data. A wid investigated considering the specific nature of counterfeit and sub-standard drugs, whose content in active substance may be rather far from the declared amount. A large span in robustness parameters was considered and a complete intermediate precision asse envisaging the possibility of transferring the method to quality control laboratories, hopefully in developing countries. Finally, the method was successfully applied to the analysis of antibiotics purchased on the informal market in Chad, am and sub-standard samples were detected. © 2007 Elsevier B.V. All rights reserved. Keywords: Counterfeit drugs; Sub-standard drugs; Liquid chromatography; Screening method; Antibiotics; Uncertainty of measurement 1. Introduction The phenomenon of production and sale of counterfeit medicines is increasing worldwide, representing a serious risk for public health. Although precise and detailed data on coun- terfeitmedicines are difficult to obtain, estimates range from around 1% of sales in developed countries to over 10% in devel- oping countries, depending on the geographical area [1–3]. Data reported in the Matrix of Drug Quality Reports by the U.S. Pharmacopeia [4] indicate that in some areas of Sub-Saharan Africa,South East Asia and Latin America counterfeits make up more than 30% of medicines. Illegal Internet sales are 50% fakes [3–4]. In developing countries pharmaceutical counterfeit- ing mainly concerns life-saving medicines such as antibiotics, ∗ Corresponding author. Tel.: +39 06 49902160; fax: +39 06 49902830. E-mail address: mariacristina.gaudiano@iss.it (M.C. Gaudiano). antimalarials, anti-tubercular and antiretroviral drugs. In cases counterfeiting consists in the absence of active sub in the presence of a low quantity of active substance or i substitution of the declared active ingredient with a chea [5]. Some of the causes of the large diffusion of pharmac counterfeiting in developing countries are lack of import and poor quality control on medicinal products at differe of the distribution chain (import, wholesalers, official an mal vendors). A medicines quality control laboratory req technology, high-specialised personnel and consistent fu seldom available in less developed countries. Sometimes they succeed in affording the high cost of such a structure, bu specific expertise for developing analytical methods for p ceutical counterfeiting detection. In this scenario, the ne simple liquid chromatographic screening methods is pre Most of the published studies on analytical methods fo terfeit drug analysis propose two approaches: the develo of very simple methods (e.g. colorimetric reactions or th 0731-7085/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jpba.2007.12.032