Falsified Samples Research Articles

Usefulness of medicine screening tools in the frame of pharmaceutical post-marketing surveillance.

The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected in Cameroon. Each sample was then analyzed by HPLC and disintegration tests. Seven additional samples from the nitro-imidazole (secnidazole, ornidazole, tinidazole) and the fluoroquinolone (levofloxacin, ofloxacin, norfloxacin, moxifloxacin) families were analyzed to mimic falsified medicines. Placebo samples that contained only inert excipients were also tested to mimic falsified samples without active pharmaceutical ingredient (API). The three screening tools implemented were: a simplified visual inspection checklist, a low-cost handheld near infrared (NIR) spectrophotometer and paper analytical devices (PADs). Overall, 61.1% of the samples that failed disintegration and assay tests also failed the visual inspection checklist test. For the handheld NIR, one-class classifier models were built to detect the presence of ciprofloxacin and metronidazole, respectively. The APIs were correctly identified in all the samples with sensitivities and specificities of 100%. However, the importance of a representative and up-to-date spectral database was underlined by comparing models built with different calibration set spanning different variability spaces. The PADs were used only on ciprofloxacin samples and detected the API in all samples in which the presence of ciprofloxacin was confirmed by HPLC. However, these PADs were not specific to ciprofloxacin since they reacted like ciprofloxacin to other fluoroquinolone compounds. The advantages and drawbacks of each screening tool were highlighted. They are promising means in the frame of early detection of SF medicines and they can increase the speed of decision about SF medicines in the context of pharmaceutical post-marketing surveillance.

Prevalence of Poor Quality Ciprofloxacin and Metronidazole Tablets in Three Cities in Cameroon.

Quality is one of the essential components of medicines and needs to be ensured to preserve the population's health. This can be achieved through post-marketing quality control of medicines and is one of the most important duties of national regulatory authorities. In collaboration with the Cameroonian National Drug Quality Control and Valuation Laboratory, the decision was made to initiate a prevalence study to assess the quality of antiinfective medicines in Cameroon. A total of 150 samples of ciprofloxacin tablets and 142 samples of metronidazole tablets were collected from 76 licensed pharmacies and 75 informal vendors in three cities in Cameroon using a random strategy wherever possible and a mystery shopper approach. Three tests were carried out on each of the samples. Visual inspection allowed to find two falsified samples (0.7%) due to lack of information about the manufacturing company, and five more samples (1.7%) were deemed to be substandard due to flaws in the product. An additional 13 samples (4.5%) failed disintegration testing, and six (2.1%) others failed high-performance liquid chromatography assay testing due to insufficient active pharmaceutical ingredient (API) content. All samples were found to contain some API. A prevalence of 7.9% substandard or falsified (SF) medicines was found. Moreover, the prevalence of outlets selling SF medicines was greater in the informal sector (26.7%) than in the formal sector (2.6%). Although the prevalence of SF medicines found was low, efforts need to be made by national regulatory authorities to monitor the pharmaceutical market more closely.

Detection of vitamin C in various falsified oral formulations using voltammetry

• Healthcare supplements are prime targets to be made into falsified products. • There is an upsurge in the purchase of vitamin C due to the COVID19 pandemic. • Voltammetry provides the ability to measure vitamin C in various oral formulations. • Tablet excipients impact the oxidation peak current and potential. • Voltammetry method identified amount of vitamin C present in falsified samples. Healthcare supplements are prime targets to be made into falsified products as they undergo less stringent regulation and can be purchased through online sites. There is an upsurge in the purchase of vitamin C due to the COVID19 pandemic which has made this product a target for falsification. Vitamin C can be available in various oral formulations and thus sample preparation is required prior to analysis. Chromatography and spectroscopy are the most widely used approaches for analysis. Therefore, this study focused on investigating if voltammetry could provide a rapid measurement approach of various formulations (normal, chewable, and effervescent tablets) of vitamin C without the need for any sample analysis. We found that tablet excipients reduce the oxidation peak current and influence the peak shape and oxidation peak potentials. This variation in the oxidation peak potential provided the ability to distinguish between the different oral formulations. Voltammetry provided the ability to conduct repeatable measurements and the solutions of the tablets were stable for 2 days for measurements. In a blinded study, voltammetry was able to identify the concentration of vitamin C present and the type of oral formulation of various falsified samples. Our findings highlight that voltammetry can be a vital technique for the determination of falsified healthcare supplements.

The study of the stability of pessaries, designed to prepare the birth canal before childbirth

An urgent problem in obstetrics and gynecology is the prevention of soft tissue ruptures during childbirth. In addition to various physical exercises aimed at increasing elasticity and muscle tone, it is necessary to use aids designed to minimize perineal injuries. For this purpose, pessaries with hyaluronic acid and phytocomplex of CO2-extracts of aloe, calendula and green tea were created.
 The aim of the work – study of the stability of the proposed extemporaneous pessaries in accordance with the requirements of the article «Suppositories and pessaries manufactured in pharmacies» of the State Pharmacopoeia of Ukraine (SPU) 2.0 and Guidelines ST-N MPH 42-4.5:2015 «Requirements for the manufacture of non-sterile drugs in pharmacies».
 Quality control of pessaries was carried out on the following indicators: description, homogeneity, pH, average weight, time of deformation, decay time, melting point, acid number, microbiological purity. To detect falsified samples, a test was performed to check the base. Biopharmaceutical studies were also performed to evaluate the release of API of phytoextracts of calendula and aloe by the method of «diffusion into agar».
 When assessing the appearance and homogeneity of pessaries, it was found that they have a yellowish color and a specific odor of cocoa butter and green tea extract. There were no patches on the longitudinal section. The pH values ranged from 3.80 to 4.50, which corresponds to the normal pH value of a woman's vagina. According to other quality indicators, such as average weight, melting point, time of complete deformation, decay time, acid number and microbiological purity, the investigated drug also fully satisfies the requirements of SPU 2.0 and Guidelines ST-N 42-4.5:2015. To detect falsified samples, a test was performed to check the base. Biopharmaceutical studies were performed to evaluate the release of API of phytoextracts of calendula and aloe by the method of «diffusion into agar». The research was conducted immediately after the manufacture of pessaries and in the process of their storage.
 The stability of extemporaneous pessaries containing hyaluronic acid and phytocomplex of CO2-extracts of aloe, calendula and green tea, intended for the preparation of the birth canal before childbirth, was studied. The main quality indicators of pessaries immediately after their manufacture and during storage have been studied. It is shown that the samples of studied pessaries fully meet the requirements of the article «Suppositories and pessaries manufactured in pharmacies» of the State Pharmacopoeia of Ukraine 2.0 and Guidelines ST-N MPH 42-4.5:2015 «Requirements for the manufacture of non-sterile drugs in pharmacies».

Detection Method of Falsified Medicines by Using a Low-Cost Raman Scattering Spectrometer Combined with Soft Independent Modeling of Class Analogy and Partial Least Squares Discriminant Analysis.

There are many reports of falsified medicines that may cause harm to patients. A rapid and simple method of identifying falsified medicines that could be used in the field is required. Although Raman scattering spectroscopy has become popular as a non-destructive analysis, few validation experiments on falsified medicines that are actually distributed on the market have been conducted. In this study, we validated a discriminant analysis using an ultra-compact, portable, and low-cost Raman scattering spectrometer combined with multivariate analysis. The medicines were three types of erectile dysfunction therapeutic tablet and one type of antifungal tablet: tadalafil (Cialis), vardenafil hydrochloride (Levitra), sildenafil citrate (Viagra), and fluconazole (Diflucan), which is sometimes advertised as female Viagra. For each medicine, the authentic standard product and products obtained by personal import via the internet (genuine or falsified) were used. Discriminant analyses were performed on the Raman spectra combined with soft independent modeling of class analogy (SIMCA) and partial least squares discriminant analysis (PLS-DA). It was possible to identify all falsified samples by SIMCA using the standard product model for all four products. Using the PLS-DA using the PLS models of the four standard products, falsified Levitra and Diflucan samples were classified correctly, although some falsified Cialis and all Viagra samples also belonged to the standard class. In this study, SIMCA might be more suitable than PLS-DA for identifying falsified medicines. A spectroscopic module that combines the low-cost Raman scattering spectroscopy with SIMCA might contribute to the rapid identification of falsified medicines in the field.

Identification of Substandard and Falsified Medicines: Influence of Different Tolerance Limits and Use of Authenticity Inquiries.

ABSTRACTSubstandard and falsified medicines have severe public health and socioeconomic effects, especially in low- and middle-income countries. The WHO has emphasized the need for reliable estimates of the prevalence of such medicines to efficiently respond to this problem. In the present study, we used 601 medicine samples collected in Cameroon, the DR Congo, and Malawi to assess the rates of substandard and falsified medicines based on different criteria. Based on the specifications of the U.S. Pharmacopoeia for the amount of the active pharmaceutical ingredients, the rate of out-of-specification medicines was 9.3%. By contrast, this rate ranged from 3.3% up to 35.0% if the tolerance limits of other pharmacopoeias or recently published medicine quality studies were used. This shows an urgent need for harmonization. Principal methods to assess the rate of falsified medicines are packaging analysis, chemical analysis, and authenticity inquiries. In the present study, we carried out an authenticity inquiry for the aforementioned medicine samples, contacting 126 manufacturers and 42 distributors. Response rates were higher for samples stated to be manufactured in Asia (52.4%) or Europe (53.8%) than for samples manufactured in Africa (27.4%; P < 0.001). One sample had been identified as falsified by packaging analysis by the local researchers and two additional ones by chemical analysis. Notably, seven additional falsified samples were identified by the authenticity inquiries. The total rate of falsified medicines resulted as 1.7%. Considerations are discussed for assessing the rates of “substandard” and “falsified” medicines in future medicine quality studies.

Falsified tadalafil tablets distributed in Japan via the internet

The adverse health effects of falsified medicines for erectile dysfunction have been reported in Japan. We purchased tadalafil (Cialis) tablets online and assessed their authenticity and quality. Of the 45 samples we tested, nine were genuine, 23 were falsified, nine were unregistered/unlicensed samples, and the authenticity of four samples could not be ascertained. Observation of packaging and tablet size, weight, and color revealed differences between some genuine and falsified samples. All genuine samples contained the active pharmaceutical ingredient tadalafil at adequate quantities, while falsified samples contained sildenafil (Viagra). Some falsified samples contained insufficient quantities of tadalafil. All unregistered/unlicensed samples contained neither tadalafil nor sildenafil. Some falsified samples did not dissolve/disintegrate sufficiently. The status of most samples was detectable by Raman scattering and near-infrared spectroscopy. Restricting consumer access to falsified medicines can prevent undesirable health effects.

Equivalence in Active Pharmaceutical Ingredient of Generic Antihypertensive Medicines Available in Nigeria (EQUIMEDS): A Case for Further Surveillance

BackgroundWidespread access to good quality antihypertensive medicines is a critical component for reducing premature cardiovascular disease (CVD) mortality. Poor-quality medicines pose serious health concerns; however, there remains a knowledge gap about the quality of cardiovascular medicines available in low- and middle-income countries. ObjectivesThe aim of this study was to determine the quality of generic antihypertensive medicines available in the retail market of a developing country. MethodsSamples of the 2 most commonly prescribed classes of antihypertensive medicines were collected from 3 states in 3 different geopolitical zones in Nigeria following a semirandom sampling framework. Medicine samples were purchased by mystery shoppers from 22 pharmacy outlets from 6 local government areas across the 3 states. Medicine quality was determined by measuring the amount of stated active pharmaceutical ingredient using high-performance liquid chromatography with photodiode array detection and classified according to their compliance to the specified pharmacopeia tolerance limits for each antihypertensive drug. ResultsAmlodipine and lisinopril were identified as the most commonly prescribed antihypertensive drugs in Nigeria. In total, 361 samples from 22 pharmacies were collected and tested. In total, 24.6% of amlodipine and 31.9% of lisinopril samples were of substandard quality and significantly more samples purchased in rural (59 of 161, 36.7%) compared with urban (32 of 200, 16%) outlets were found to be of substandard quality (p < 0.001). No falsified samples of either amlodipine or lisinopril were detected. There was large variation in price paid for the antihypertensive medicines (range ₦150 to ₦9,750). Of the 24 pharmacy outlets surveyed, 46% stated that patients did not always require a prescription and 21% had previously reported a medicine as falsified or substandard. ConclusionsMore than one-quarter of some commonly prescribed antihypertensive medicines available in Nigeria may be of substandard quality. Enhanced quality assurance processes in low- and middle-income countries, such as Nigeria, are needed to support optimum management.

Comparison of hyperspectral imaging techniques for the elucidation of falsified medicines composition

Hyperspectral imaging has shown a high potential to analyze falsifications of solid pharmaceutical products since the last decade. Thanks to the non-destructive, ecological and non-invasive properties, it is a preferred technique for these kinds of applications. Moreover, thanks to the spectroscopic properties, it is possible to detect as well organic compounds as inorganic compounds in a single analysis. Therefore, we recommend using it as second-line laboratory analysis technique. Raman microscopy and Fourier Transform Infrared (FT-IR) microscopy are two interesting techniques that are complementary. In this study, the potential of the two hyperspectral imaging techniques is evaluated to elucidate the composition of falsified antimalarial tablets. Hyperspectral data are analyzed by Multivariate Curve Resolution-Alternating Least Square (MCR-ALS). The results obtained from this study show that Raman hyperspectral imaging seems to be more suited to detect low dosed compounds possibly due to a smallest sampling volume. It has been also possible to link formulations of falsified samples of two different brands.

Application of differential scanning calorimetry in the analysis of apprehended formulations of anabolic androgenic steroids

Over the past ten years, there has been a significant increase in the amount of formulations containing anabolic androgenic steroids apprehended worldwide. A considerable amount of these illicit preparations is falsified imposing a series of challenges for the analytical identification of alleged active ingredients due to the presence of interferers. In this sense, the aim of this work was to identify and quantify the active ingredient using cholesterol as internal standard in eight apprehended formulations of anabolic androgenic steroids in either tablet, capsule or injectable forms employing visual inspection and instrumental analysis of Fourier Transform Infrared Spectroscopy, Gas Chromatography — Mass Spectrometry and Differential Scanning Calorimetry. The assessed samples were kindly provided by the Brazilian Federal Police as representative samples from an apprehension made in July of 2017. Qualitatively, 25% of the analyzed materials were determined to be falsified as they were composed of excipients only while the others had the alleged active ingredient confirmed. However, after quantitative analysis, the majority of samples were placed as counterfeit materials as the active substance was found in concentrations lower than stated in the label. Preliminary visual inspection provided important information to distinguish genuine from falsified samples. It should be noted that this work was one of the few available reports to employ Differential Scanning Calorimetry in the analysis of anabolic agents, which proved to be an important complementary tool for the detection of the active ingredient, when present, along with the calorimetric profile of the formulations studied. Fourier Transform Infrared Spectroscopy and Gas–Chromatography — Mass Spectrometry were also efficient analytical tools in order to identify and to characterize substances present in fraudulent preparations.

Microwave-assisted extraction and differential scanning calorimetry in the chemical identification of sliming agents apprehended in the south region of Brazil

Over the past decades, consume of slimming agents considerably increased in several countries, including Brazil, due to weight-loss and stimulant properties. Since these drugs are controlled to prevent illicit and indiscriminate use, there is a parallel illegal market that uses the Internet and irregular pharmacies in order to distribute these formulations. Slimming agents produced by these illegal sources are known for being manufactured with little or none quality control resulting in uncertain and unknown formulations. For forensic purposes, apprehended pharmaceuticals have to undergo a process of chemical identification that can be difficult due to its complex matrix. In this sense, application of assisted energies in the extraction step such as microwave irradiation can be a promising method to increase the recuperation of the target molecules of the sample. Therefore, the aim of this research was to identify four slimming agents apprehended in Brazil by means of visual inspection, Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry and Gas Chromatography – Mass Spectrometry. Moreover, the efficiency of solid-liquid extraction and microwave-assisted extraction was compared. It should be noted that our work was one of the few to use Differential Scanning Calorimetry and the application of microwave irradiation in the analysis of apprehended materials. Results showed that the majority of the samples was counterfeit being composed of one or several adulterants or contaminants. Initially, visual inspection resourcefully screened the slimming agents for possible signs of falsification, however it failed to detect fraudulent products that were very similar to veridical medicines. Sequentially, Fourier Transform Infrared Spectroscopy detected functional groups present in the samples while the presence or absence of the alleged active ingredients were successfully measured with Differential Scanning Calorimetry and, thus, providing a full chemical screening of the apprehended materials. Gas Chromatography- Mass Spectrometry confirmed the presence of adulterants such as caffeine, fluoxetine and phenolphthalein as well as contaminants such as sulfurol in the falsified samples. Finally, comparison of extraction procedures indicated that microwave-assisted extraction increased the recovery of compounds detected in chromatographic analysis to a greater extent than solid-liquid extraction.

Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market

Advances in biotechnology and the chemical synthesis of peptides have made biopharmaceuticals and synthetic peptide drugs viable pharmaceutical compounds today and an important source for tomorrow's drugs and therapies. Unfortunately, also falsifications and counterfeit versions of these powerful and promising drugs are offered illegally via the internet. Since these falsified preparations are produced outside the legally required quality systems, end-users have no guarantee regarding the efficacy and safety of these products. Although falsified samples of biotherapeutics were already analysed, looking at a specific aspect of their quality or identity, no systematic studies have been performed regarding the presence of different impurities or possible contaminations. Therefore, in order to obtain a better understanding of the potential health risks related to the usage of falsified polypeptide drugs we performed a systematic screening of the ten most frequently encountered falsified peptide drugs on the Belgian market acquired from three different suspected illegal internet pharmacies. The screening incorporated the analysis of the active pharmaceutical ingredient (API), API-related impurities, small molecule contaminants (defined as organic small molecules not belonging to the other categories), elemental impurities and residual solvents. This comprehensive study showed that these type of falsified drugs not only have a high variation in amount of drugs per unit and a low purity (ranging between 5% and 75% for cysteine containing peptides), but also contained the known toxic class one elemental impurities arsenic (As) and lead (Pb). One sample was contaminated with Pb while multiple samples were found with concentrations up to ten times the ICH toxicity limit for parenteral drugs. Subsequent speciation of As confirmed the elevated concentrations for As and demonstrated that all As was present in the more toxic inorganic form. Together with the (sometimes) high amount of peptide impurities and the inherent dangers associated with the use of unauthorized peptide drugs (such as doping peptides or preclinical drugs) this study confirms the reported potential health risks patients/users take when resorting to falsified peptide drugs. Moreover, the presence of the carcinogen As and the known accumulation in human tissues of Pb raises questions about potential sub-acute to chronic toxicity due to the long term administration of these falsified peptide drugs.

Raman chemical imaging for spectroscopic screening and direct quantification of falsified drugs

Falsified drugs are a threat to the health of patients. The analytical control of such products contributes to the fight against this global issue. Raman chemical imaging is a method that relies on consecutive measurements at the surface of a sample, combining spectroscopy, microscopy and chemometrics. This article explores the capabilities of this analytical technique proposing an innovative methodology with spectroscopic screening for the identification of chemical compounds and the direct quantification of the active substance (without prior calibration). Two chemometric methods were used: Multivariate Curve Analysis − Alternate Least Squares for the qualitative analysis and Direct Classical Least Squares for the quantitative analysis. The methodology was optimized with samples prepared in the laboratory and validation parameters were studied. The methodology was then applied to real (authentic and falsified) samples of Viagra® and Plavix®. Despite the presence of fluorescence emission in some samples, the methodology succeeded in the detection of active pharmaceutical ingredients, and in the discrimination of three salts of clopidogrel (in generic formulations of Plavix®). The quantitative deviation from the reference method ranged from −15% to +24% of the active substance content. This deviation may be considered to be acceptable since it is sufficient for assessing the risk to the health of patients and for quickly alerting the health authorities.

Of quality indicators determination and study of the stability of pessaries with acyclovir and essential oils

An important issue in modern pharmaceutical practice is the creation of new combined medicines for topical treatment of genital herpes. Aim. To determine the quality indicators and study the stability of developed pessaries with acyclovir and essential oils of tea tree and thyme in accordance with the requirements of SPU 2.0. Materials and methods. The homogeneity was determined in accordance with SPU. The quantitative content of acyclovir in 1 pessary, in grams, is in the range from 0.180 to 0.220. To identify falsified samples of pessaries, a test on the base was introduced: the difference between the hydrophilic base and the hydrophobic base. Determination of the pH of the aqueous solution of pessaries was carried out according to the procedure of SPU p. 2.2.3 “Potentiometric determination of pH”. The determination of the average mass of samples of pessaries was carried out on 20 pessaries in accordance with the requirements of SPU 2.0. The deviation is not more than ± 5 %. Tests on the disintegration of pessaries were carried out on a device for determining the disintegration of suppositories and pessaries of PHARMA TEST. Results. Based on the results of the work, the methods of quality control project was developed, which included the following indicators: characteristic, identification, homogeneity, pH, average mass, disintegration time, microbiological purity, quantitative determination of acyclovir. Conclusions. The stability of pessaries on 5 series of samples was studied and the shelf life during 15 months was established. Studies on the stability of pessaries continue.

A New Handheld Device for the Detection of Falsified Medicines: Demonstration on Falsified Artemisinin-Based Therapies from the Field.

Poor-quality medicines are a major problem for health-care systems in resource-poor settings as identifying falsified medicines requires a complex laboratory infrastructure such as a Medicines Quality Control Laboratory. We report here an evaluation of a low-cost, handheld near-infrared spectrometer (NIRS) device by analyzing a library of artemisinin-based combination therapy (ACT) medicines to determine its usefulness as a drug-screening tool. The “SCiO” research prototype device was used to collect NIR spectra of a library of ACT and artesunate monotherapy medicine samples previously collected in Bioko Island and Equatorial Guinea and Kintampo, Ghana. The quality of these samples had been categorized as falsified, substandard, and quality assured based on the amount of stated active pharmaceutical ingredients detected using high-performance liquid chromatography photodiode array. Numerical analyses were performed on the NIR spectra to assess the usefulness of NIR to identify falsified and substandard medicines. The NIRS device was successful at detecting falsified medicines in all cases where the library contained both quality assured and falsified medicines of the same stated brand of medicines. The NIRS device was successful at identifying substandard amounts of artesunate but not amodiaquine in the ACT samples (N = 15) of artesunate–amodiaquine. This work reveals that this low-cost, portable NIRS device is promising for screening ACTs for falsified samples and could enable widespread drug screening at all points of the health system.

A 1H NMR-based metabolomics approach to evaluate the geographical authenticity of herbal medicine and its application in building a model effectively assessing the mixing proportion of intentional admixtures: A case study of Panax ginseng: Metabolomics for the authenticity of herbal medicine

Ginseng, the root of Panax ginseng has long been the subject of adulteration, especially regarding its origins. Here, 60 ginseng samples from Korea and China initially displayed similar genetic makeup when investigated by DNA-based technique with 23 chloroplast intergenic space regions. Hence, 1H NMR-based metabolomics with orthogonal projections on the latent structure-discrimination analysis (OPLS-DA) were applied and successfully distinguished between samples from two countries using seven primary metabolites as discrimination markers. Furthermore, to recreate adulteration in reality, 21 mixed samples of numerous Korea/China ratios were tested with the newly built OPLS-DA model. The results showed satisfactory separation according to the proportion of mixing. Finally, a procedure for assessing mixing proportion of intentionally blended samples that achieved good predictability (adjusted R2=0.8343) was constructed, thus verifying its promising application to quality control of herbal foods by pointing out the possible mixing ratio of falsified samples.

Determinación de cobre y zinc en muestras falseadas de latón. Niveles de abertura como propuesta de enseñanza de la técnica de titulación complexométrica

This article presents a study that involves related concepts to complexometric titration, an application method of inorganic analysis, using the framework of a pedagogical technique called Levels of Openness of Inquiry, based on a form of active learning that emphasizes questioning, data analysis, and critical thinking. The purpose of this study was to develop higher cognitive processes in which students do something fairly complex with what they are learning, from knowledge, understanding and application to the analysis, synthesis and evaluation of related information with processes of various types of analytical methods. The laboratory practice used was the complexometric determination of copper and zinc in a falsified sample practice (spiked) of brass. The use of falsified samples offers a good variant in the teaching of complexometric titration processes. Thus, this writing offers teachers a proposal of didactic intervention that combines Levels of Openness, cooperative learning and falsified samples designed to teach neglected topics in this area. It also offers students the opportunity to transform a signifier into signified. This study shows favorable results to the learning process in a group of in service teachers involved in a Master program in chemistry teaching at Pedagogica Nacional University in Bogota.

Determinación de cobre y zinc en muestras falseadas de latón. Niveles de abertura como propuesta de enseñanza de la técnica de titulación complexométrica

This article presents a study that involves related concepts to complexometric titration, an application method of inorganic analysis, using the framework of a pedagogical technique called Levels of Openness of Inquiry, based on a form of active learning that emphasizes questioning, data analysis, and critical thinking. The purpose of this study was to develop higher cognitive processes in which students do something fairly complex with what they are learning, from knowledge, understanding and application to the analysis, synthesis and evaluation of related information with processes of various types of analytical methods. The laboratory practice used was the complexometric determination of copper and zinc in a falsified sample practice (spiked) of brass. The use of falsified samples offers a good variant in the teaching of complexometric titration processes. Thus, this writing offers teachers a proposal of didactic intervention that combines Levels of Openness, cooperative learning and falsified samples designed to teach neglected topics in this area. It also offers students the opportunity to transform a signifier into signified. This study shows favorable results to the learning process in a group of in service teachers involved in a Master program in chemistry teaching at Pedagogica Nacional University in Bogota.