Characterization of Prototype Gummy Formulations Provides Insight into Setting Quality Standards.

Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness for persons of different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing six brands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028 mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829 mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5 g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this work contribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.

Integrated spectroscopic approaches for the facile one pot quantification of olanzapine in pharmaceutical formulation and spiked human plasma.

In this work, the xanthene dye, erythrosine B, was employed as a probe for the determination of olanzapine using two fast and highly simple analytical approaches. The assay was based on the formation of a binary complex between the drug and erythrosine B in a slightly acidic aqueous buffered solution. In the first method, the absorbance of the formed product was monitored at 558 nm. The reaction stoichiometry was investigated, and the stability constant of the formed complex was estimated. The linear range of the method that obeyed Beer's law was in the concentration range of 0.6-8.0 µg/ml. The calculated detection and quantitation limits were 0.2 and 0.6 µg/mL. Upon adding the drug solution to erythrosine B, the native fluorescence of the dye was quenched and monitored at 550 nm after excitation at 528 nm. Thus, the fluorescence quenching was utilized as the quantitative signal in the spectrofluorimetric approach. The extent of quenching in the fluorescence intensity was rectilinear with the drug concentration in a range of 0.1-2.5 µg/ml with a detection limit of 0.032 µg/ml. Both approaches were analytically validated based on the guiding rules of the ICH with acceptable results, and were utilized efficiently in the analysis of olanzapine in commercial tablets containing the cited drug. In addition, owing to its high sensitivity and selectivity, the spectrofluorimetric method was applied for drug analysis in spiked human plasma with satisfactory % recoveries. Finally, the greenness of the methods was confirmed using eco-score scale and Analytical Green Evaluation metrics.

A Case Study Demonstrating the Importance of Glass Vial Selection for Parenteral Pharmaceutical Products.

There are many factors to consider when selecting a container closure system for parenteral drug products to maintain their quality, efficacy, and safety. One aspect to consider for products stored in glass vials is the glass type. Although the glass vials in which most parenteral products are stored are classified as Type I by the United States Pharmacopoeia, Chapter <660>, not all glass vials that meet the glass performance characteristics of Type I are equivalent. In the study presented here, Type I glass vials from three suppliers of three different Type I glass vials (standard, delamination control, and coated) were investigated to evaluate the impact that each Type I glass vial had on the stability of a drug product under development. To evaluate this impact, a three-phase study was conducted in which the compatibility between the drug product and each vial was assessed through the measurement of the critical quality attributes of the product, extractable and leachable inorganic elements were analyzed for each vial, and finally a stability study under accelerated conditions was conducted for the drug product in the most compatible vial based on the aforementioned experiments. Results from this study demonstrated that there are, in fact, significant differences in glass vials regardless of their classification as Type I. In the study conducted here, delamination control Type I glass vials were found to be superior to both Standard Type I and coated Type I vials for the drug product under investigation.

Microchip isotachophoresis for green and sustainable pharmaceutical quality control: Method validation and application to complex pharmaceutical formulations.

Universal microchip isotachophoresis (µITP) methods were developed for the determination of cationic and anionic macrocomponents (active pharmaceutical ingredients and counterions) in cardiovascular drugs marketed in salt form, amlodipine besylate and perindopril erbumine. The developed methods are characterized by low reagent and sample consumption, waste production and energy consumption, require only minimal sample preparation and provide fast analysis. The greenness of the proposed methods was assessed using AGREE. An internal standard addition was used to improve the quantitative parameters of µITP. The proposed methods were validated according to the ICH guideline. Linearity, precision, accuracy and specificity were evaluated for each of the studied analytes and all set validation criteria were met. Good linearity was observed in the presence of matrix and in the absence of matrix, with a correlation coefficient of at least 0.9993. The developed methods allowed precise and accurate determination of the studied analytes, the RSD of the quantitative and qualitative parameters were less than 1.5% and the recoveries ranged from 98 to 102%. The developed µITP methods were successfully applied to the determination of cationic and anionic macrocomponents in six commercially available pharmaceutical formulations.

A Comprehensive Examination of UV-VIS Spectrophotometric Methods in Pharmaceutical Analysis Between 2015-2023.

BACKGROUND: Quality control is a system of validated procedures in which many samples, including active pharmaceutical ingredients and final products, are analyzed using standard or validated analytical methods. METHOD: Analytical methods used in analyzing active pharmaceutical ingredients or final products in the pharmaceutical industry can be methods registered in pharmacopeias and developed by the company itself. For this reason, published papers related to pharmaceutical analysis attract analysts and researchers' attention. In this study, pharmaceutical analysis and bioanalysis studies carried out between 2015 and 2023 were examined using Google Scholar, and the recent trends were determined for pharmaceutical analysis. Among the published papers performing conventional analytical techniques for pharmaceutical analysis, those applying UV-VIS spectrophotometry method were selected to predict a future perspective in this study. In addition to the data obtained, the current situation of the pharmaceutical industry was considered to correlate with the obtained data for pharmaceutical analysis. RESULTS: The results were presented with comparative tables and summarizing graphs. Interpreting the results allowed us to determine the trends that pharmaceutical analysis studies will lead in the future. This study can be helpful for researchers working on pharmaceutical analysis in both the industry and academia to predict future trends in pharmaceutical analysis. As a result of the literature research covering the dates 2015-2023, 56% of UV-VIS Spectrophotometric methods are used on pharmaceutical dosage forms, 27% are bulk, 16% are pure, 2% are biological materials, and 0.4% are herbal. Made from materials. Of these studies, 28% were conducted in the 200-240 nm range, 27% were conducted in the 240-300 nm range, and only 44% were conducted at >300 nm. Interpreting the results allowed us to determine the trends that pharmaceutical analysis studies will lead in the future. CONCLUSION: This study can be helpful for researchers working on pharmaceutical analysis in both the industry and academy side to predict future trends for pharmaceutical analysis.

[Transformation of scientific research results into teaching resources to improve the teaching effect: taking the teaching of the chromatographic method in the pharmaceutical analysis course as an example].

The pharmaceutical analysis course is a three-dimensional knowledge network that connects several courses to form a new comprehensive knowledge node involving a large knowledge system and flexible knowledge structure. In this course, the subject of chromatography covers a wide range of topics. However, because accurate content is challenging to present, the teaching effect of this subject is poor. In this work, we sought to achieve the educational purpose of establishing morality and cultivating talent, as well as the goal of training highly skilled professionals, by taking the teaching of chromatography in the pharmaceutical analysis course as an example of transforming scientific research results into teaching resources. The resources obtained are integrated into the teaching process to provide innovative and scientific research ideas to students with the aim of not only helping them understand and master technical knowledge but also exercise their ability to raise and solve problems. Furthermore, we expound on how to introduce scientific development frontiers and formulate scientific problems through curriculum design. We also describe how our strategy can promote the teaching effect and achieve teaching objectives. Based on the characteristics of rapid knowledge update and equal emphasis on theory and practice in pharmaceutical analysis, the course is designed by introducing new advances in scientific development, formulating scientific problems, and adopting question- and problem-based learning methods for teaching. The teaching effect is then evaluated through diversified assessment, student feedback, and self-evaluation. The results show that the transformation of scientific research results into teaching resources plays a significant role in stimulating students' interest in learning, improving students' ability to solve problems, and achieving curriculum objectives, all of which greatly improve the teaching effect.

Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform.

Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.

Deep eutectic solvents as green and sustainable diluents in headspace gas chromatography for the determination of trace level genotoxic impurities in pharmaceuticals.

Genotoxic impurities (GTIs) are potential carcinogens that need to be controlled down to ppm or lower concentration levels in pharmaceuticals under strict regulations. The static headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD) is an effective approach to monitor halogenated and nitroaromatic genotoxins. Deep eutectic solvents (DESs) possess tunable physico-chemical properties and low vapor pressure for HS-GC methods. In this study, zwitterionic and non-ionic DESs have been used for the first time to develop and validate a sensitive analytical method for the analysis of 24 genotoxins at sub-ppm concentrations. Compared to non-ionic diluents, zwitterionic DESs produced exceptional analytical performance and the betaine : 7 (1,4- butane diol) DES outperformed the betaine : 5 (1,4-butane diol) DES. Limits of detection (LOD) down to the 5-ppb concentration level were achieved in DESs. Wide linear ranges spanning over 5 orders of magnitude (0.005-100 µg g-1) were obtained for most analytes with exceptional sensitivities and high precision. The method accuracy and precision were validated using 3 commercially available drug substances and excellent recoveries were obtained. This study broadens the applicability of HS-GC in the determination of less volatile GTIs by establishing DESs as viable diluent substitutes for organic solvents in routine pharmaceutical analysis.

A Selective Gas Chromatography-Tandem Mass Spectrometry Method for Quantitation of Ethylene and Diethylene Glycol in Paediatric Syrups.

Ethylene Glycol (EG) and diethylene Glycol (DEG) are two contaminants known to cause various human health problems. These glycols might be present in drug syrups that are based on glycerol, sorbitol, or polyethylene glycol. In late 2022, several batches of cough, antipyretics, and antihistamine syrups were reported to contain toxic levels of EG and DEG in multiple countries; this incident concerned the World Health Organization (WHO). From an analytical perspective, several methods of glycols analysis in pharmaceuticals have been reported in the literature, with the majority being dedicated to raw material analysis. This study aims to develop a selective method capable of evaluating a wide range of paediatric syrups in order to assess the safety of commercially available paediatric syrups currently distributed in the local market. This research introduces a method for determining glycols utilizing gas chromatography-tandem mass spectrometry (GC-MS/MS), which offers significantly higher selectivity than conventional single quadrupole gas chromatography-mass spectrometry (GC-MS). The developed method meets the current International Council for Harmonisation (ICH) guidelines for validation. The absence of any interfering peaks in both the unspiked sample of promethazine syrup and the reference standard solutions proved the method's selectivity. Furthermore, 2,2,2-trichloroethanol was used as an internal standard, and a new GC-MS/MS method was developed to analyze it. The calibration curves for EG and DEG were linear within the selected concentration range of 1-10 µg/mL. The detection limit for both EG and DEG was 400 ng/mL, while the quantification limit was 1 µg/mL. Recovery values for both EG and DEG met the accuracy acceptance criterion. Thus, the developed method proved to be efficient and accurate for determining EG and DEG levels in suspected contaminated syrups.

Nanomaterials as catalysts for the sensitive and selective determination of diclofenac.

Background and purpose: Diclofenac (DCF) is a non-steroidal anti-inflammatory drug possessing analgesic and antipyretic properties. It is used for the treatment of rheumatoid arthritis pain, osteoarthritis, and acute muscle pain conditions and can be administrated orally, topically or intravenously. Because of its widespread use, hydrophilicity, stability and poor degradation (bioaccumulation in the food chain), DCF is an emerging chemical contaminant that can cause adverse effects in the ecosystems. Taking into account the consumption of DCF in pharmaceutical formulations and its negative impact on the environment, the development of new sensitive, selective, cheap, fast, and online capable analytical devices is needed for on-site applications. Experimental approach: This brief review attempts to cover the recent developments related to the use of nanomaterials as catalysts for electrochemical determination of DCF in pharmaceutical formulations, biological fluids and environmental samples. Key results: The article aims to prove how electrochemical sensors represent reliable alternatives to conventional methods for DCF analysis. Conclusion: The manuscript highlights the progress in the development of electrochemical sensors for DCF detection. We have analyzed numerous recent papers (mainly since 2019) on sensors developed for the quantitative determination of DCF, indicating the limit of detection, linear range, stability, reproducibility, and analytical applications. Current challenges related to the sensor design and future perspectives are outlined.

A non-extraction sequential injection method for determination of loratadine using formation of its ion-association complex with bromocresol purple in acetonitrile.

The formation of an ion-association complex (IA) between sulfonephthalein dye and basic nitrogen-containing compound in an organic solvent medium has been for the first time used to develop an automated SIA method. In highly polar aprotic solvents, the tautomeric equilibrium for such dyes is strongly shifted towards the colorless lactonic form. The addition of a basic nitrogen-containing substance leads to the formation of IA with a highly colored quinonoid form, which is accompanied by an increase in the absorbance of the dye band at approximately 400 nm. Protonation of pyridine nitrogen in loratadine, structure and binding places of IA were shown using quantum-chemical calculations. The very simple, direct and non-extraction spectrophotometric SIA method with high throughput of 43 h-1 was developed based on the formation of IA between loratadine and bromocresol purple in the medium of acetonitrile used both as solvent and carrier. The calibration graph was linear in the concentration range from 1.0 to 20 mg L-1 with correlation coefficient of 0.9992. The developed method was successfully applied to the analysis of pharmaceutical formulations.

Implications of analytical nanoscience in pharmaceutical and biomedical fields: A critical view.

This review summarizes recent progress performed in the design and application of analytical tools and methodologies using nanomaterials for pharmaceutical analysis, and specifically new nanomedicines at distinct phases of development and translation from preclinical to clinical stages. Over the last 10-15 years, a growing number of studies have utilized various nanomaterials, including carbon-based, metallic nanoparticles, polymeric nanomaterials, materials based on biological molecules, and composite nanomaterials as tools for improving the analysis of pharmaceutical products. New and more complex nanomaterials are currently being explored to influence different stages of the analytical process. These materials provide unique properties to support the extraction of analytes in complex samples, increase the selectivity and efficiency of chromatographic separations, and improve the analytical properties of many sensor applications. Indeed, nanomaterials, including electrochemical detection approaches and biosensing, are expanding at a remarkable rate. Furthermore, the analytical performance of numerous approaches to determine drugs in different matrices can be significantly improved in terms of precision, detection limits, selectivity, and time of analysis. However, the quality control and metrological characterization of the currently synthesized nanomaterials still depend on the development of new and improved analytical methodologies, and the application of specific and improved instrumentation. Therefore, there is still much to explore about the properties of nanomaterials which need to be determined even more precisely and accurately.

An eco-friendly one-pot spectrofluorimetric approach for the facile determination of overactive bladder drug, tolterodine: Application to dosage forms and biological fluids.

Tolterodine tartrate (TTD) was the first antimuscarinic medication developed exclusively for the treatment of overactive bladder syndrome and was approved by the FDA in 1998. As a result of the drug's extensive utilization within the local community following its authorization, there is a pressing need to develop and validate a spectrofluorometric method that is economically efficient, easily reproducible, environmentally sustainable, and possesses high sensitivity. The developed approach relies on enhancing the fluorescence intensity of TTD to reach a level 720 % higher than its initial value, achieved through the application of an aqueous sodium dodecyl sulfate (SDS) solution. A strong correlation was observed with a correlation coefficient of 0.9998 between the concentration of TTD and the fluorescence intensity within the range of 25.0-500.0 ng mL-1. This approach could be employed to quantify TTD in its pure form and to examine pharmaceutical tablets for the purposes of verifying uniform content. Additionally, it was utilized for the evaluation of TTD concentrations in spiked human plasma.

Enantioselective separation and determination of ibuprofen: Stereoselective pharmacokinetics, pharmacodynamics and analytical methods.

Ibuprofen (IBP), the 29th most prescribed drug in the United States in 2019, is a widely used nonsteroidal anti-inflammatory drug (NSAID) comprising two enantiomers, (R)-IBP and (S)-IBP, collectively known as (RS)-IBP. This critical review examines analytical techniques for the enantioselective separation and determination of IBP enantiomers, crucial for pharmaceutical and clinical applications. The review focuses on state-of-the-art methods, including chromatographic techniques including high-performance liquid chromatography, gas chromatography, liquid chromatography-tandem mass spectrometry, and some other techniques. This review addresses pharmacokinetics, pharmacology, and side effects of each enantiomer, ensuring safe drug usage. By consolidating diverse analytical methods and their applicability in different matrices, this review serves as a valuable resource for researchers, analysts, and practitioners in pharmaceutical analysis, pharmacology, and clinical studies.

3D-printed extraction devices fabricated from silica particles suspended in acrylate resin.

In recent years, there has been an increasing worldwide interest in the use of alternative sample preparation methods. Digital light processing (DLP) is a 3D printing technique based on using UV light to form photo-curable resin layer upon layer, which results in a printed shape. This study explores the application of this technique for the development of novel drug extraction devices in analytical chemistry. A composite material consisting of a photocurable resin and C18-modified silica particles was employed as a sorbent device, demonstrating its effectiveness in pharmaceutical analysis. Apart from estimating optimal printing parameters, microscopic examination of the material surface, and sorbent powder to resin ratio, the extraction procedure was also optimised. Optimisation included the type and amount of sample matrix additives, desorption solvent, sorption and desorption times, and proper number of sorbent devices needed in extraction protocol. To demonstrate this method's applicability for sample analysis, the solid-phase extraction followed by gas chromatography coupled with mass spectrometry (SPE-GC-MS) method was validated for its ability to quantify benzodiazepine-type drugs. This evaluation confirmed good linearity in the concentration range of 50-1000 ng/mL, with R2 values being 0.9932 and 0.9952 for medazepam and diazepam, respectively. Validation parameters proved that the presented method is precise (with values ranging in-between 2.98 %-7.40 %), and accurate (88.81 % to 110.80 %). A negative control was also performed to investigate possible sorption properties of the resin itself, proving that the addition of C18-modified silica particles significantly increases the extraction efficiency and repeatability. The cost-effectiveness of this approach makes it particularly advantageous for single-use scenarios, eliminating the need for time-consuming sorbent-cleaning procedures, common in traditional solid-phase extraction techniques. Future optimisation opportunities include refining sorbent size, shape, and geometry to achieve lower limits of quantification. As a result of these findings, 3D-printed extraction devices can serve as a viable alternative to commercially available SPE or solid-phase microextraction (SPME) protocols for studying new sample preparation approaches.

What is the role of current mass spectrometry in pharmaceutical analysis?

The role of mass spectrometry (MS) has become more important in most application domains in recent years. Pharmaceutical analysis is specific due to its stringent regulation procedures, the need for good laboratory/manufacturing practices, and a large number of routine quality control analyses to be carried out. The role of MS is, therefore, very different throughout the whole drug development cycle. While it dominates within the drug discovery and development phase, in routine quality control, the role of MS is minor and indispensable only for selected applications. Moreover, its role is very different in the case of analysis of small molecule pharmaceuticals and biopharmaceuticals. Our review explains the role of current MS in the analysis of both small-molecule chemical drugs and biopharmaceuticals. Important features of MS-based technologies being implemented, method requirements, and related challenges are discussed. The differences in analytical procedures for small molecule pharmaceuticals and biopharmaceuticals are pointed out. While a single method or a small set of methods is usually sufficient for quality control in the case of small molecule pharmaceuticals and MS is often not indispensable, a large panel of methods including extensive use of MS must be used for quality control of biopharmaceuticals. Finally, expected development and future trends are outlined.

LC-MS/MS Investigation of nitrosamine impurities in certain Sartan group medicinal products available in Istanbul, Türkiye.

Nitrosamines (NAs) are molecules that include the nitroso functional group. In 2018, the US Food and Drug Administration (FDA) received its first report of NAs in pharmaceuticals. The fact that NA impurities are likely human carcinogens is relevant to these compounds. Furthermore, prolonged exposure to NA contaminants above safe limits may raise the risk of cancer. The goal of this article was to assess the amounts of six different NAs in Sartan group medicines purchased from formal pharmacies in Istanbul, Türkiye, using a validated LC-MS/MS assay. An LC-MS/MS-based analytical assay was undertaken. The separation was performed with a HR ODS 150mm×3.0mm and 5-analytical columns, providing effective separation of major peaks from NA impurities. In mobile phase A, formic acid was 0.10% in water, while in mobile phase B, formic acid was 0.10% in methanol. The flow rate was 0.4mL/minute, and the total runtime was 18minutes with the gradient elution mode. The validation was conducted in line with ISO/IEC 17025 requirements. Up to 100µg/L, linearity was determined using correlation coefficients (r2>0.995) for all NAs. The limit of quantification values for all NAs analyses were below 1.0µg/L. The mean recovery value obtained during the spike experiment was 95.18%, demonstrating the accuracy of the procedure. In addition, the accuracy was shown by a certified reference analysis, which yielded relative standard deviation and relative error values of 1.82% and 3.34%, respectively. During the intermediate precision testing, bias and relative standard deviation were 0.96 and 2.87%, respectively. Of the 75 study samples involving Sartan group medical products, no nitrosamine impurities were detected, demonstrating that pharmaceutical companies have adequate medication safety precautions in place in accordance with FDA and European Medicines Agency (EMA) regulations published to prevent NA contaminants in human medicinal products.

Current Applications of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) in Pharmaceutical Analysis: Review.

The present review encompasses various applications of multivariate curve resolution- alternating least squares (MCR-ALS) as a promising data handling, which is issued by analytical techniques in pharmaceutics. It involves different sections starting from a concise theory of MCR-ALS and four detailed applications in drugs analysis. Dissolution, stability, polymorphism, and quantification are the main four detailed applications. The data generated by analytical techniques associated with MCR-ALS deals accurately with different challenges compared to other chemometric tools. For each reviewed purpose, it was explained how MCR-ALS was applied and detailed information was given. Different approaches were introduced to overcome challenges that limit the use of MCR-ALS efficiently in pharmaceutical mixture were also discussed.

Quality testing of mifepristone and misoprostol in 11 countries.

OBJECTIVE: Previous studies have demonstrated quality concerns with misoprostol. Mifepristone, however, has not been extensively assessed for quality. Between 2020 and 2021, Concept Foundation and the International Planned Parenthood Federation conducted a study to determine the quality of these medical abortion drugs in low- and middle-income countries (LMIC). METHODS: The collection of batch samples of misoprostol and mifepristone was carried out by trained sampling agents in selected LMIC. Single drug packs and combipacks were sampled. A World Health Organization prequalified laboratory conducted testing method verifications and subsequent sample analysis. Tests included identification, assay, related substances, and content uniformity for misoprostol, and identification, assay, related substances, and dissolution for mifepristone. RESULTS: Samples were collected from Burkina Faso, Cambodia, Democratic Republic of Congo, India, Kyrgyzstan, Moldova, Nepal, Nigeria, Pakistan, Uganda and Vietnam. Sixty-four pooled batch samples were tested, consisting of 31 combipacks, 26 misoprostol-only and seven mifepristone-only products. Overall, 54.7% of samples were non-compliant with one or more of the specifications, representing 51.6% of combipack products, 57.1% of misoprostol tablets analyzed and 23.7% of mifepristone tablets. One falsified misoprostol-only product was found. CONCLUSION: The present study confirms that a significant problem still exists in relation to the quality of medical abortion drugs in LMIC. For misoprostol, our findings suggest that historical concerns around primary packaging may have been largely resolved but that manufacturing processes for both finished product and active pharmaceutical ingredient need to be improved. The present study also provides evidence of mifepristone quality issues.

Tools to Evaluate the Eco-efficiency of Analytical Methods in the Context of Green and White Analytical Chemistry: A Review.

BACKGROUND: The release of a product in the consumer market requires an analysis by quality control. This sector makes use of reliable analytical methods, by high performance liquid chromatography (HPLC), spectrophotometry in the ultraviolet and visible regions (UV-Vis), spectrophotometry in the infrared region (IR) or thin layer chromatography (TLC), for example, to reach a result. The analysis conditions of most of these analytical methods currently still use toxic reagents, generate a greater amount of waste, sample preparation has more steps, the need for instrumentation and consumables in greater quantity, generating a cost and impact on health and the environment greater than if there were adoption of the Green Analytical Chemistry (GAC) and the White Analytical Chemistry (WAC). OBJECTIVE/METHODS: The objective of this review is to show the relationship of analytical choices for current pharmaceutical analyzes with the GAC and the WAC. RESULTS: Analytical methods can be evaluated for greenness and whiteness using tools such as the National Environmental Method Index (NEMI), Eco-Scale Assessment (ESA), Analytical Greenness Metric (AGREE) and Green Analytical Procedure Index (GAPI). CONCLUSION: The use of NEMI, ESA, AGREE and GAPI tools brings the objective evidence needed to discuss the greenness and whiteness of an analytical method, leaving the subjective level. Furthermore, semi or quantitative data facilitate the choice of an analytical method and its conditions, when the target is the concern with eco-efficiency.