Analytical Methods For Quality Control Research Articles

Validation of Analytical Methods for Quality Control of Gel for Dentin Remineralization

Introduction. As a result of a complex of scientific and experimental studies carried out at the Department of Pharmaceutical Technology of the State Pharmacy of Pharmaceuticals, a gel was developed for remineralization of dentin in order to carry out drug treatment of medium and deep caries. In the developed gel, along with the remineralizing effect, an antibacterial effect was achieved, which is necessary in the treatment of dentin caries due to the introduction of chlorhexidine bigluconate (CHB). The proposed composition simultaneously contains the main remineralizing ions – calcium, phosphate and fluoride in a free active state. Due to this, a significant increase in their penetration into the dentin is ensured. During the preparation of regulatory documentation for the gel for the treatment of dentine caries, validation of methods designed to control the quality of active substances was carried out.Aim. Validation of methods for testing the authenticity and quantification of active substances in the gel for dentine remineralization.Materials and methods. To achieve this goal, active pharmaceutical substances of pharmacopoeial quality are used. When developing test methods, pharmacopoeial and non-pharmacopoeial reactions to reacting cations and anions were used. For the quantitative determination of the chloride compound, the complexometric method, the back titration method is used, for potassium phosphate, the disubstituted acidimetric method, for sodium fluoride, the photoelectrocolorimetric method, for chlorhexidine bigluconate, the lauryl sulfate method. The objects of study were five serial samples of gels.Results and discussion. As a result of the studies, methods of testing for authenticity were developed, it was found that the proposed methods are characterized by a negative analytical signal on model mixtures free of the analyte and placebo, and a positive analytical signal on model mixtures of various compositions containing the analyte. The validation characteristics of methods for the quantitative determination of active substances in the gel were studied, positive results were obtained, the proposed methods can be used for inclusion in the regulatory documentation for the developed gel.Conclusion. When evaluating the validation characteristics of the proposed methods, it was found that the methods of testing for authenticity and quantitative determination of active substances in the gel are specific, the methods of quantitative determination are characterized by accuracy and repeatability, a linear dependence in the analytical region of ±20 % of the declared amount of active substances, which allows them to be used for reliable assessment of the quality of the developed gel.

Identification of Major Bioactive Anti-inflammatory Compounds of Derris scandens Stem Using RAW 264.7 Cells and HPLC-UV Analysis.

Derris scandens (DS) is widely recognized for its therapeutic properties, specifically its analgesic effects, which significantly alleviate muscle pain. The chemical constituents of DS stem include various isoflavone derivatives. However, there is currently a lack of specified anti-inflammatory chemical markers and analytical methods for quality control. The present study aimed to evaluate the anti-inflammatory activity of DS and its constituents using the RAW 264.7 cell model. The expression of inflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and 5-lipoxygenase (5-LOX) was examined using quantitative RT-PCR. An high-performance liquid chromatography with a UV detection method was developed to quantitatively analyze genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside, genistein, derrisisoflavone A, lupalbigenin, and 6,8-diprenylgenistein in DS stem. The developed HPLC-UV method demonstrated high sensitivity with limits of detection and quantification ranging from 0.01 to 0.06 µg/mL and 0.03 to 0.18 µg/mL, respectively. The accuracy of the method ranged from 93.3 to 109.6%. Furthermore, the repeatability and reproducibility of the method were suitable, as indicated by the relative standard deviations of ≤ 3.02% and ≤ 6.22%, respectively. The DS extract notably inhibited NO production, exhibiting effects comparable to those of 500 µM diclofenac, and substantially suppressed the expression of iNOS, COX-2, IL-6, and 5-LOX of lipopolysaccharide (LPS)-induced genes. As to the pure isoflavone derivatives, the order of NO production inhibition was found to be genistein > lupalbigenin > derrisisoflavone A > 6,8-diprenylgenistein > genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside. Genistein, derrisisoflavone A, and 6,8-diprenylgenistein significantly suppressed the upregulation of all LPS-induced genes. Consequently, these compounds are recommended as anti-inflammatory markers for the quantitative chemical analysis of DS.

Development and validation method for the determination of related substances in nimesulide granules for oral suspension

One of the key stages of pharmaceutical development is the development of analytical methods for quality control of medicines. The critical quality indicator is the content of related impurities, which may increase during shelf life of the product due to the degradation of the active substance, which in turn affects the quality of the product. The aim of the work is to develop and validate the method for the determination of related impurities in nimesulide granules for oral suspension by HPLC method; to set the specification of finished product for related impurities. Materials and methods. Sample of finish product Nimesulide, granules for oral suspension, 100 mg/2 g, it was manufactured by JSC “Farmak”. The study was performed using Agilent 1260 liquid chromatograph with UV detector. 2-phenoxyaniline from Sigma-Aldrich, reference standards of nimesulide impurity D EP CRS and LGC, Nimesulide for peak identification EP CRS were used for preparation of standard impurity solutions. Acetonitrile and ammonium dihydrogen phosphate from Sigma-Aldrich were used for chromatographic analysis. Results. When developing method, the concentrations of solutions, the method of dissolving granules, filters were selected. The chromatographic column was selected, the requirements for the chromatographic system suitability were set. The effect of placebo components has been studied and considered. During the validation the characteristics were studied: specificity, linearity, LOD, LOQ, precision, accuracy, robustness. The limits of the impurity content were established in accordance with the requirements of ICH Q3B guideline, taking into account the data of stress studies, stability and impurities of the substance. Conclusions. The analytical method for the determination of related substances in finish product nimesulide granules for oral suspension was developed. The validation results showed that the method is suitable for analysis. The specification limits of finished product for related impurities were set.

Automated Synthesis of 68Ga-Labeled DOTA-MGS8 and Preclinical Characterization of Cholecystokinin-2 Receptor Targeting.

The new minigastrin analog DOTA-MGS8 targeting the cholecystokinin-2 receptor (CCK2R) used in this study displays the combination of two site-specific modifications within the C-terminal receptor binding sequence together with an additional N-terminal amino acid substitution preventing fast metabolic degradation. Within this study, the preparation of 68Ga-labeled DOTA-MGS8 was validated using an automated synthesis module, describing the specifications and analytical methods for quality control for possible clinical use. In addition, preclinical studies were carried out to characterize the targeting potential. [68Ga]Ga-DOTA-MGS8 showed a high receptor-specific cell internalization into AR42J rat pancreatic cells (~40%) with physiological expression of rat CCK2R as well as A431-CCK2R cells transfected to stably express human CCK2R (~47%). A favorable biodistribution profile was observed in BALB/c nude mice xenografted with A431-CCK2R cells and mock-transfected A431 cells as control. The high tumor uptake of ~27% IA/g together with low background activity and limited uptake in non-target tissue confirms the potential for high-sensitivity positron emission tomography of stabilized MG analogs in patients with MTC and other CCK2R-related malignancies.

Создание и валидация способа количественного определения бисопролола в новой фармакологической композиции "Бисопролозоль"

Introduction. When developing new pharmacologically active compositions and introducing them into extemporaneous manufacturing and industrial production, a comprehensive study of the properties of the medicinal product applying modern methods of analysis combining high metrological characteristics, expressiveness, sensitivity, accuracy, availability, reliability is mandatory. Development of analytical methods for quality control of new drug compositions is an urgent task of modern pharmaceutical analysis. Aim. Development and validation of a method for quantitative determination of bisoprolol in a new pharmacological composition "Bisoprolozol". Material and methods. To perform the analysis, we used pharmaceutical substance bisoprolol fumarate, glycerol hydrophilic gel "Tizol", ointment "Bisoprolozol" consisting of 0,5% of selective beta-blocker in titanium-containing glycerohydrogel. During the experiment, spectrophotometer SF-2000 and the method of absorption spectrophotometry in the ultraviolet region were used. Regression analysis of data obtained was performed in Microsoft Office Excel 2016 (OFS.1.1.0013.15 "Statistical processing of the results of chemical experiment"). The technique was evaluated according to validation parameters: specificity, linearity, correctness, and precision. Results. Studying the electronic spectral curves of bisoprolol we determined that its analysis is rationally performed at a wavelength of 274 nm (experimentally determined maximum absorption). In the course of the study we determined the sensitivity of the determination of the drug, which is equal to 5.260 µg/ml at A(min) = 0.02. The results of quantitative analysis of bisoprolol in the pharmacological composition "Bisoprolozol" showed that the mass of the selective blocker of adrenergic receptors (0.0409-0.0536 g) is within the acceptable limits according to the regulatory documentation for soft pharmaceutical forms (Order of the Russian Ministry of Health № 751n of 26.10.2015). Conclusion. In the present experiment, optimal conditions for the spectrophotometric method of analysis were selected, based on which the method of quantitative determination of bisoprolol in the new pharmacological composition "Bisoprolozol" with an error not exceeding ± 1.89 % was developed, validated and presented.

World Health Organization guidelines on transfer of analytical methods of quality control for medical preparation

This review contains the recommendations of the World Health Organization for the transfer of analytical methods of quality control for medical preparation. Due to the absence of the Russian documents describing in detail the technology transfer process, pharmaceutical developers and manufacturers should refer to international guidelines. One of the main documents which fully describes the process of pharmaceutical technologies transfer is World Health Organization guidelines on transfer of technology in pharmaceutical manufacturing. The recommendations are presented both for the transfer of medical preparation manufacturing and transfer of analytical methods for quality control for a medical preparation. This review contains the recommendations for the transfer of analytical methods only.

DNA Metabarcoding for Quality Control of Basil, Oregano, and Paprika.

Herbs and spices are some of the most vulnerable products in terms of fraud and adulteration in the food sector. Although standard analytical methods are accurate for quality control of specific lead or marker compounds, they cannot accurately assess the entire species composition of many marketed products. Complementary analytical approaches are thus often used for comprehensive screening of herbs and spices. In this study we evaluate DNA metabarcoding for the identification and authentication of 62 products, containing basil, oregano, and paprika collected from different retailers and importers in Norway. Our results show varying degrees of discrepancy between the constituent species and those listed on the product labels, despite high product authenticity. We suggest the false positives result from the sensitivity of DNA metabarcoding and filtering thresholds should be integrated into protocols to reduce false positives. Our results highlight how integrating DNA metabarcoding into the toolbox of analytical methods for quality control of fresh and/or processed plant-based food can improve product quality.

Synthesis and analysis of 4-(3-fluoropropyl)-glutamic acid stereoisomers to determine the stereochemical purity of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) for clinical use.

(4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is a positron emission tomography (PET) imaging agent for measuring the system xC- transporter activity. It has been used for the detection of various cancers and metastasis in clinical trials. [18F]FSPG is also a promising diagnostic tool for evaluation of multiple sclerosis, drug resistance in chemotherapy, inflammatory brain diseases, and infectious lesions. Due to the very short half-life (110 min) of 18F nuclide, [18F]FSPG needs to be produced on a daily basis; therefore, fast and efficient synthesis and analytical methods for quality control must be established to assure the quality and safety of [18F]FSPG for clinical use. To manufacture cGMP-compliant [18F]FSPG, all four nonradioactive stereoisomers of FSPG were prepared as reference standards for analysis. (2S,4S)-1 and (2R,4R)-1 were synthesized starting from protected L- and D-glutamate derivatives in three steps, whereas (2S,4R)-1 and (2R,4S)-1 were prepared in three steps from protected (S)- and (R)-pyroglutamates. A chiral HPLC method for simultaneous determination of four FSPG stereoisomers was developed by using a 3-cm Chirex 3126 column and a MeCN/CuSO4(aq) mobile phase. In this method, (2R,4S)-1, (2S,4S)-1, (2R,4R)-1, and (2S,4R)-1 were eluted in sequence with sufficient resolution in less than 25 min without derivatization. Scale-up synthesis of intermediates for the production of [18F]FSPG in high optical purity was achieved via stereo-selective synthesis or resolution by recrystallization. The enantiomeric excess of intermediates was determined by HPLC using a Chiralcel OD column and monitored at 220 nm. The nonradioactive precursor with >98% ee can be readily distributed to other facilities for the production of [18F]FSPG. Based on the above accomplishments, cGMP-compliant [18F]FSPG met the acceptance criteria in specifications and was successfully manufactured for human use. It has been routinely prepared and used in several pancreatic ductal adenocarcinoma metastasis-related clinical trials.

Sensory Analysis – A contemporary Quality Control tool for Asava-Arishta

Quality control of Ayurvedic medicines though being the need of the hour, is an arduous task. As Ayurveda encompasses the use of drug as a whole which leads to generation of a complex matrix. In such a scenario, selective and sensitive sophisticated analytical tools alone cannot serve the purpose. Besides, the ancient science of medicine is sensory driven. A number of sensory based quality standards in form of quality-attributes for drugs as well as critical end point for pharmaceutical operations are mentioned in the classics of Ayurveda. It is thus advisable to employ sensory based analytical methods for Quality control of Ayurvedic medicines. Henceforth, in the present study an attempt was made to develop a sensory based Quality control tool for discrimination of the market samples of Arjunaristha with regards to In-house prepared (Reference control) sample on the basis of smell and taste. Among the sensory methods available, Duo-Trio method was adopted. 40 pre-trained assessors were asked to identify the blindly coded sample analogous to Reference control. The results were analysed using Receiver Operating Characteristics (ROC) curve, Area Under Curve (AUC) and d-prime (d’) with the help of sensR package in R-studio ver. 1.0.143. In both the sample sets, Reference control sample was correctly identified with a significance level of P < 0.001 and Area Under Curve of 0.999 and 0.994 for each set respectively. Thus, it can be concluded that Sensory analysis method efficiently discriminated the Arjunaristha samples and thus can serve as a cost-effective routine quality control tool.

Integrated metabolomics and network pharmacology strategy for ascertaining the quality marker of flavonoids for Sophora flavescens

Traditional Chinese medicines (TCMs) have been widely used in Asian countries for thousands of years due to their supreme quality and good clinical efficacy. However, the increasing demand for TCMs in recent decades warrants effective quality control methodology to avoid clinical problems. Therefore, comprehensive quality evaluation systems should be established for ensuring TCM's quality, in terms of chemical components, as well as bioactivity for identifying quality markers in TCM and developing suitable analytical methods for quality control. In this study, we selected Sophora flavescens (S. flavescens) as the research object and developed a novel integrated strategy combining metabolomics and network pharmacology to explore the quality markers. Firstly, we determined the targeted metabolomic profiles of seventy-four batches of S. flavescens (aged from 1 to 6 years) by UHPLC/QE-MS. Six potential markers were successfully screened, quantified and reverse-verified as the most influential effective compounds by UHPLC/QE-MS and multivariate statistical analysis. Secondly, the network of "components-targets-pathways" was constructed, and the pharmacological activities of six potential markers were predicted. Finally, we determined the anti-tumor activity of six flavonoids (kurarinone, norkurarinone, kuraridin, kushenol N, trifolirhizin, and genistein) as the quality markers for Sophora flavescens, evaluated their pharmacokinetic profiles and reviewed their existing pharmacological researches. Thus, integrated metabolomics and network pharmacology technology were applied for the effective discovery of quality markers of Chinese material medica.

Pharmaceutical compounding of orphan active ingredients in Belgium: how community and hospital pharmacists can address the needs of patients with rare diseases

BackgroundPharmaceutical compounding of orphan active ingredients can offer cost-effective treatment to patients when no other drug product is available for a rare disease or during periods of drug product shortages. Additionally, it allows customized therapy for patients with rare diseases. However, standardized compounding formulas and procedures, and monographs are required to ensure the patients’ safety.ResultsStandardized formulas and compounding procedures were developed for seven orphan active ingredients (L-arginine, sodium benzoate, sodium phenylbutyrate, L-carnitine, chenodesoxycholic acid, primaquine phosphate, pyridoxal phosphate) and one non-orphan molecule (sodium perchlorate) regularly compounded by hospital pharmacists for extemporaneous use. The stability of these formulations was evaluated over 3 months at refrigerated (5 °C) and standard storage conditions (25 °C/60%RH) using HPLC-based assays and a suitable shelf life was assigned to the formulations. Additionally, suitable analytical methods for quality control of formulations of pyridoxal phosphate and sodium perchlorate were developed as monographs for these components were not available in the European Pharmacopeia or United States Pharmacopeia.ConclusionsAvailability of compounding formulas and protocols, as well as stability information, for orphan active ingredients can improve patients’ access to treatment for rare diseases. Such data were collected for seven orphan active ingredients to treat patients with rare diseases when no other treatment is available. More efforts are needed to develop standardized formulas and compounding procedures for additional orphan active ingredients whose clinical efficacy is well-known but which are not available as products with a marketing authorization. Additionally, a legal framework at EU level is required to enable the full potential of pharmaceutical compounding for orphan active ingredients.

Authenticity investigation of bovine tallow for biodiesel production via mass spectrometry: a comparison with traditional methodology

Biodiesel has emerged as a promising alternative to fossil fuels due to advantages related to sustainability and reduction of polluting gases emission and, in Brazil, the main raw materials used by biodiesel industry are soybean oil and bovine tallow, however, bovine tallow stands out due to its low cost, supply without competition with food market, high calorific value, high number of cetanes, and most importantly, because of its 100% conversion rate. It is produced by transesterification or esterification process of triglycerides with low content of free fatty acids or raw material rich in free fatty acids in the presence of a catalyst. The extensive usage of bovine tallow in biodiesel production values it, and similar to important commodities, it has also been frequently adulterated with the addition of specific products (frying residual oils and other animal fats from industrial by-products) decreasing the raw material quality. Consequently, there is a need for fast and reliable analytical methods for quality control. Therefore, this work evaluated the lipid quality of bovine tallow provided by biodiesel industry to confirm its authenticity; fatty acid composition was obtained by gas chromatography coupled with flame ionization detector. The lipid profile was obtained by fingerprint applying direct electrospray ionization mass spectrometry. Additionally, the lipid profile obtained for bovine tallow samples were compared with the lipid profiles obtained for soybean oil, poultry oil and a standard bovine tallow. Conclusively, fraud in bovine tallow by poultry oil was observed in one sample.

The use of analytical methods for quality control of promising active pharmaceutical ingredients among derivatives of 4-oxoquinoline- 3-propanoic acids

Due to a global increase of microbial resistance to antimicrobial drugs the search for new antibiotics is vital for modern medicinal chemistry. 3-Quinolin-4-one propanoic acids have the molecular similarity with fluoroquinolone antibiotics and are prospective scaffold to create antimicrobial drugs. On the example of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid the analytical methods that can be used for quality control of promising active pharmaceutical ingredients (API) among derivatives of 3-(2-methyl-4 oxo-1,4-dihydroquinoline-3-yl) propanoic acids have been analyzed and tested. The necessity of their inclusion in the list of control methods of 13C NMR-spectroscopy, due to which the problem of the tautomeric forms of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid is uniquely solved, has been shown. Specific related substances, which are by-products of the synthesis of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid – 1,2,3,4,9,10- hexahydroacridine-2,9-dione and 6a-hydroxy-5,6,6a, 8,9,14,15,16a, 17,18-decahydro-7,16-dioxa -5.14-diazaheptacene-9,18-dione, have been identified using liquid chromatography-mass spectrometry (LC-MS/MS). Recommendations for the use of UV- and IR-spectroscopy to develop quality control methods for 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid have been proposed.

Improved non-invasive Optical Coherence Tomography detection of different engineered nanoparticles in food-mimicking matrices

Food industry and regulators require fast and reliable analytical methods for quality control. This especially counts for the detection of engineered nanomaterials (ENMs) in food products. Respective EU regulation is in force, but the development of appropriate methods is still underway. This paper updates the scope of Optical Coherence Tomography (OCT) for ENM/food matrix analysis. A range of nanomaterials and composites – Au@SiO2, Ag, Ag@SiO2 and SiO2 – in a simplified food matrix was investigated. The earlier finding of linear dependencies between concentration in the dispersion and light responses could be reproduced. Being able to analyse non-invasively for a relevant industrial compound such as SiO2, makes OCT an excellent candidate for screening purposes.

Characteristic fragmentation behavior of tobacco‐specific N‐nitrosamines using electrospray ionization multistage tandem mass spectrometry incorporating deuterium labeling

Tobacco-specific N-nitrosamines (TSNAs) mainly include 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonornicotine (NNN), N-nitrosoanabasine (NAB) and N-nitrosoanatabine (NAT) that are formed from tobacco alkaloids during the curing process and contained in tobacco and tobacco smoke. They are linked with carcinogenesis. Analytical methods for quality control of products and determination of their metabolites are therefore of great importance. The characteristic fragmentation behaviors of tobacco-specific TSNAs have been studied by electrospray ionization multistage tandem mass spectrometry. The deutero-labeled TSNA compounds have also been employed to clarify the fragmentation mechanism, which further confirms the proposed fragmentation patterns. Detailed analysis of the resultant fragments shows there are two different kinds of fragmentation patterns with the general fragment backbone of pyrrolidine or piperidine rings. In one route, pyrrolidine or piperidine rings undergo direct fragmentation and form some stable intermediates without affecting the parent rings. The other, however, involves ring opening and then ring closure at the pyridine-2 carbon atom to form multi-membered rings. This characteristic fragmentation behavior therefore provides useful information on identification of TSNAs that may be used to monitor such kinds of compound in the biological metabolism.

Avaliação de procedimentos para quantificação espectrofotométrica de flavonoides totais em folhas de Bauhinia forficata link

Interest in analytical methods for quality control of herbal drugs has grown sharply due to the scarcity of monographs in official manuals. Thus, the aim of the present study was to evaluate analytical procedures for quantitative determination of flavonoids from leaves of Bauhinia forficata Link (pata-de-vaca). Two procedures for quantification of total flavonoids (with and without acid hydrolysis) by spectrophotometry were tested. The proposed methods proved to be specific, sensitive, precise, accurate and robust, being suitable for routine laboratory use.

Analysis of Asbestos and Mineral Elements in Talci Pulvis from Different Habitats with the Methods of SEM-EDXA and ICP-AES

Talci Pulvis (huashifen) is a powder prepared from Talcum by sorting, cleaning, pulverizing, and drying according to Chinese Pharmacopeoa (2010 edition, Part I). It is mainly distributed in Guangxi, Jiangxi, Qinghai, Shandong, and Liaoning provinces in China. Talci Pulvis can be divided into nine types such as the first type for cosmetics, the second type for medicine and food, the third type for paint et al. according to its different application. It contains main components of hydrous magnesium silicate and the trace elements of Fe, Al and Ca et al. Asbestos, a cancerigenic chemical ingredient, was associated in Talci Pulvis in some reports recently years. So it is very important to set up some analytical methods for quality control of Talci Pulvis.

Production, characterization and development of standards for biodiesel — A review

Biodiesel is being promoted worldwide as a supplement and alternative automotive fuel for petroleum diesel in spite of several technological, economical and social barriers. This has provided an impetus for new research to overcome these deterrents in its production, to establish its quality criteria (standards), and to develop superior analytical methods for quality control and quality assessment of biodiesel in production and entire distribution chain until consumed by end user. The present review paper briefly covers the production, characterization and standardization of biodiesel, having relevance to the preparation of certified reference materials (CRMs) of biodiesel.

A qualitative and quantitative HPTLC densitometry method for the analysis of cannabinoids in Cannabis sativa L.

Cannabis and cannabinoid based medicines are currently under serious investigation for legitimate development as medicinal agents, necessitating new low-cost, high-throughput analytical methods for quality control. The goal of this study was to develop and validate, according to ICH guidelines, a simple rapid HPTLC method for the quantification of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and qualitative analysis of other main neutral cannabinoids found in cannabis. The method was developed and validated with the use of pure cannabinoid reference standards and two medicinal cannabis cultivars. Accuracy was determined by comparing results obtained from the HTPLC method with those obtained from a validated HPLC method. Delta(9)-THC gives linear calibration curves in the range of 50-500 ng at 206 nm with a linear regression of y = 11.858x + 125.99 and r(2) = 0.9968. Results have shown that the HPTLC method is reproducible and accurate for the quantification of Delta(9)-THC in cannabis. The method is also useful for the qualitative screening of the main neutral cannabinoids found in cannabis cultivars.

Analysis of illegally manufactured formulations of tadalafil (Cialis ®) by 1H NMR, 2D DOSY 1H NMR and Raman spectroscopy

Counterfeit and/or imitation medicines are becoming a major health problem not only in developing countries but also in wealthier countries. The need of new and easy analytical methods for quality control of drugs is essential. We describe the use of Raman spectroscopy, 1H nuclear magnetic resonance (NMR) and 2D diffusion-ordered spectroscopy (DOSY) NMR to analyse genuine Cialis ® and seven illegally manufactured formulations of this drug purchased via the internet. Seven out of the eight commercial formulations of tadalafil contain the active ingredient, measured by high performance liquid chromatography (HPLC), within 100 ± 5% of stated concentration. Vardenafil and homosildenafil instead of tadalafil were found in the Chinese imitation. 2D DOSY NMR spectra clearly showed similarities and differences in the composition of the pharmaceutical formulations of tadalafil, thus giving a precise and global “signature” of the manufacturer. Our data show that the quality of the Cialis imitations manufactured in India and Syria is correct, whereas the Chinese formulation is adulterated with active pharmaceutical ingredients.