Ambient mass spectrometry technologies for the detection of falsified drugs

Increased globalization of the pharmaceutical market has facilitated the unobstructed and fast spread of poor-quality medicines. Poor-quality medicines include spurious/falsely-labeled/falsified/counterfeit drugs (those that are deliberately and fraudulently mislabeled with respect to content and/or origin), substandard drugs (legitimate drugs that do not meet their quality specifications), and degraded medicines (good quality pharmaceuticals that suffered from deterioration caused by improper storage or distribution). Consumption of poor-quality pharmaceuticals is likely to increase morbidity and mortality.Moreover, poor-quality drugs can also contribute to the development of resistance to anti-infective medicines and decrease the quality of health care received by patients. To assess the true prevalence of poor quality drugs, tiered technology approaches enabling the testing of drug samples collected at points of sale are required, thus ensuring public health standards. High throughput and high resolution ambient mass spectrometry techniques allow investigation of pharmaceuticals with minimal or no sample preparation, thus possessing capabilities to survey a large number of drug samples for their authenticity.Fil: Culzoni, Maria Julia. Georgia Institute Of Techology; Estados Unidos. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; ArgentinaFil: Dwivedi, Prabha. Georgia Institute Of Techology; Estados UnidosFil: Green, Michael D.. Centers For Disease Control And Prevention. National Center For Infectious Diseases. Division Of Parasitic Diseases; Estados UnidosFil: Newton, Paul. Mahosot Hospital; Laos. University of Oxford; Reino UnidoFil: Fernandez, Facundo. Georgia Institute Of Techology; Estados Unido

Novel Polyoxometalate- Ionic Liquid with Antibacterial and Antifungal Properties. Feasibility of Its Implementation As a Multifunctional Thin Coating

The synthesis of hybrid materials, combining the properties of organic and inorganic components, results in composites with unique physical and chemical features. Polyoxometalates (POMs), i.e. inorganic anionic molecular metal oxides, are considered as promising future metallodrugs due to their antiviral, antitumoral and antibacterial activities. The combination of bulky organic cations with POMs results in composite ionic liquids (IL; melting point below 100°C) which combine the unique properties of both components. Pioneering studies have used composites of alkylammonium cations and POM anions for multifunctional water purification to remove toxic heavy materials, organic aromatics and microbes and for the inhibition of bio-corrosion on metal and stone surfaces due to coating formation.Fil: Enderle, Ana Gabriela. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Streb, C.. Universitat Ulm; AlemaniaFil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Culzoni, Maria Julia. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química. Cátedra de Química Analítica; ArgentinaFil: Mitchell, S. G.. Universidad de Zaragoza; EspañaFil: Franco Castillo, I.. Universidad de Zaragoza; España2019 AIChE Annual MeetingOrlandoEstados UnidosAmerican Institute of Chemical Engineer

Applications of liquid-phase microextraction procedures to complex samples assisted by response surface methodology for optimization

This review presents applications of liquid phase microextraction (LPME) for extracting analytes in complex samples. This process has been introduced to simplify the extraction methods, and enhance the selectivity, sample cleanup and efficiency, allowing the extraction of a wide variety of analytes. The revision was focused on those works in which the performance of the technique was optimized by the response surface methodology (RSM). Firstly, a description of the different LPME systems is presented. Then, a brief explanation of the most popular tools applied for optimization is displayed. After that, the results of a literature search of the works reported from 2009 to 2019 based on the implementation of microextraction supported by experimental design and optimization can be found summarized in a table. Finally, an illustrative example providing the necessary information to carry out this kind of work is presented. A list of the most popular software available to apply RSM is also presented.Fil: Carabajal, Maira Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Teglia, Carla Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Cerutti, Estela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Culzoni, Maria Julia. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; Argentin

Bioaccumulation of abacavir and efavirenz in Rhinella arenarum tadpoles after exposure to environmentally relevant concentrations

Antiretrovirals are pharmaceuticals used in the treatment of the human immunodeficiency virus; they are contaminants of emerging concern that have received considerable attention in recent decades due to their potential negative environmental effects. Data on the bioaccumulation and possible environmental risks posed by these drugs to aquatic organisms are very scarce. Therefore, the aim of this study was to evaluate the bioaccumulation of abacavir and efavirenz in Rhinella arenarum tadpoles subjected to acute static toxicity tests (96 h) at environmentally relevant concentrations. The analytical procedure consisted of the development and optimization of a method involving ultra-high performance liquid chromatography with tandem mass spectrometry detection. The instrumental conditions, optimized by design of experiments using the response surface methodology, yielded limits of detection of 0.3 μg L−1 for abacavir and 0.9 μg L−1 for efavirenz; and limits of quantification of 1.9 μg L−1 for abacavir and 5.6 μg L−1 for efavirenz. Subsequently, the bioaccumulation of the pharmaceutical drugs in tadpoles was evaluated at three exposure concentrations. Efavirenz displayed the highest bioaccumulation levels. This study shows the bioaccumulation potential of abacavir and efavirenz in amphibian tadpoles at exposure concentrations similar to those already detected in the environment, indicating an ecological risk for R. arenarum and probably other aquatic organisms exposed to these drugs in water bodies.Fil: Paradina Fernández, Lesly Anniled. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Brasca, Romina. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Repetti, María Rosa. Universidad Nacional del Litoral; ArgentinaFil: Attademo, Andres Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Peltzer, Paola. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Lajmanovich, Rafael Carlos. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Culzoni, Maria Julia. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentin

Prevalence of substandard and falsified artemisinin-based combination antimalarial medicines on Bioko Island, Equatorial Guinea.

INTRODUCTION: Poor-quality artemisinin-containing antimalarials (ACAs), including falsified and substandard formulations, pose serious health concerns in malaria endemic countries. They can harm patients, contribute to the rise in drug resistance and increase the public's mistrust of health systems. Systematic assessment of drug quality is needed to gain knowledge on the prevalence of the problem, to provide Ministries of Health with evidence on which local regulators can take action. METHODS: We used three sampling approaches to purchase 677 ACAs from 278 outlets on Bioko Island, Equatorial Guinea as follows: convenience survey using mystery client (n=16 outlets, 31 samples), full island-wide survey using mystery client (n=174 outlets, 368 samples) and randomised survey using an overt sampling approach (n=88 outlets, 278 samples). The stated active pharmaceutical ingredients (SAPIs) were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. RESULTS: Content analysis showed 91.0% of ACAs were of acceptable quality, 1.6% were substandard and 7.4% falsified. No degraded medicines were detected. The prevalence of medicines without the SAPIs was higher for ACAs purchased in the convenience survey compared with the estimates obtained using the full island-wide survey-mystery client and randomised-overt sampling approaches. Comparable results were obtained for full island survey-mystery client and randomised overt. However, the availability of purchased artesunate monotherapies differed substantially according to the sampling approach used (convenience, 45.2%; full island-wide survey-mystery client, 32.6%; random-overt sampling approach, 21.9%). Of concern is that 37.1% (n=62) of these were falsified. CONCLUSION: Falsified ACAs were found on Bioko Island, with the prevalence ranging between 6.1% and 16.1%, depending on the sampling method used. These findings underscore the vital need for national authorities to track the scale of ineffective medicines that jeopardise treatment of life-threatening diseases and value of a representative sampling approach to obtain/measure the true prevalence of poor-quality medicines

Quality of artemisinin-based combination formulations for malaria treatment: prevalence and risk factors for poor quality medicines in public facilities and private sector drug outlets in Enugu, Nigeria.

BACKGROUND: Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. METHODS: ACAs were purchased using three sampling approaches--convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. RESULTS: Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. CONCLUSION: Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained

Determination of loratadine and pseudoephedrine sulfate in pharmaceuticals based on non-linear second-order spectrophotometric data generated by a pH-gradient flow injection technique and artificial neural networks

Loratadine (LOR) and pseudoephedrine sulfate (PES) were determined in pharmaceutical samples by using non-linear second-order data generated by a pH-gradient flow injection analysis (FIA) system with diode-array detection. Determination of both analytes was performed on the basis of differences between the acid-base and spectral features of each drug species. Non-linearities were detected by using both qualitative and quantitative tools. As a consequence of the non-linearity, a recently reported algorithm, artificial neural networks followed by residual bilinearization (ANN/RBL), was shown to furnish more satisfactory results. Recoveries of 99.7% (LOR) and 95.6% (PES) were obtained when analyzing a validation set containing unexpected components (the usual excipients found in pharmaceutical preparations). The average value obtained by implementation of the method on four replicates was compared with that obtained by a reference method based on HPLC (difference not significant; p > 0.05).Fil: Culzoni, Maria Julia. Laboratorio de Desarrollo Analítico y Quimiometría (ladaq); Argentina. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goicoechea, Hector Casimiro. Laboratorio de Desarrollo Analítico y Quimiometría (ladaq); Argentina. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Multiway Calibration Approaches for Quality Control of Food Samples

Nowadays, the use of modern instruments in analytical laboratories is generating a large varietyof second- and higher-order instrumental data, that is, instead of obtaining a scalar for eachsample measurement as when, for example, one absorbance at one wavelength is registered, amatrix tensor (second-order data) or a cube tensor (third-order data) of data points is recordedfor each sample under analysis. Interestingly, an enhancement in the analytical properties isobtained by processing the latter data, which have made multiway calibration a subject of highinterest for the analytical community, producing a significant impact on the development ofanalytical methods, especially for the quantitation of analytes of interest in complex matrices,such as those found in environmental, biological, and food samples, among others.Modeling second- and higher-order data allows one to exploit the remarkable and wellknownsecond-order advantage (Escandar et al., 2014). This means that an analytical methoddeveloped employing proper second- or higher-order data modeling can quantitate analytesof interest in complex systems even in the presence of unmodeled substances (i.e., potentialinterferences). This means that no physical separation is required for quantitation givingraise to methods consuming less laboratory effort, for example, time, money, and complexinstrumentation, among others. In addition, second and higher-order calibration methodsbecome an attractive choice in the field of quality control laboratories due to the improvementin sensitivity and selectivity.Fil: Brasca, Romina. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Culzoni, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; Argentin

Enhanced fluorescence sensitivity by coupling yttrium-analyte complexes and three-way fast high-performance liquid chromatography data modeling

The present study reports a sensitive chromatographic method for the analysis of seven fluoroquinolones (FQs) in environmental water samples, by coupling yttrium-analyte complex and three-way chromatographic data modeling. This method based on the use of HPLC-FSFD does not require complex or tedious sample treatments or enrichment processes before the analysis, due to the significant fluorescence increments of the analytes reached by the presence of Y3+. Enhancement achieved for the FQs signals obtained after Y3+ addition reaches 103- to 1743-fold. Prediction results corresponding to the application of MCR-ALS to the validation set showed relative error of prediction (REP%) values below 10% in all cases. A recovery study that includes the simultaneous determination of the seven FQs in three different environmental aqueous matrices was conducted. The recovery studies assert the efficiency and the accuracy of the proposed method. The LOD values calculated are in the order of part per trillion (below 0.5 ng mL-1 for all the FQs, except for enoxacin). It is noteworthy to mention that the method herein proposed, which does not include pre-concentration steps, allows reaching LOD values in the same order of magnitude than those achieved by more sophisticated methods based on SPE and UHPLC-MS/MS.Fil: Alcaraz, Mirta Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Culzoni, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Spectrofluorimetry in organized media coupled to second-order multivariate calibration for the determination of galantamine in the presence of uncalibrated interferences

The present article describes the spectrofluorimetric determination of galantamine, a widely usedacetylcholinesterase inhibitor, through excitation–emission fluorescence matrices and second-order calibration. With the purpose of enhancing the fluorescence intensity of this substance, the effect of different organized assemblies was evaluated. Although the interaction of galantamine with different cyclodextrins is weak, it was corroborated that the fluorescence intensity of this pharmaceutical in the presence of -cyclodextrin is increased by a twofold factor. Among the studied micellar media, the anionic surfactant sodium dodecyl sulfate produced the largest signals for the compound of interest (sixfold enhancement), and was selected as auxiliary reagent for the subsequent determinations. The developed approachenabled the determination of galantamine at the ngmL−1 level without the necessity of applying separation steps, and in the presence of uncalibrated interferences. The applied second-order chemometric tools were parallel factor analysis (PARAFAC), unfolded partial least-squares coupled to residual bilinearization (U-PLS/RBL), and multidimensional partial least-squares coupled to residual bilinearization (N-PLS/RBL). The ability of U-PLS/RBL to successfully overcome spectral interference problems is demonstrated. The quality of the proposed method was established with the determination of galantamine in both artificial and natural water samples.Fil: Culzoni, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Aucelio, Ricardo Q.. Pontifícia Universidade Católica do Rio de Janeiro; BrasilFil: Escandar, Graciela Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin