Detection Of Counterfeit Drugs Research Articles

Development and validation of a quantitative minilab system for quality evaluation of selected medicines: Albendazole, arthemether-lumefantrine combination (Co-artem®), and mebendazole finished pharmaceutical products

AbstractThe current technologies for substandard and counterfeit drug detection are either too expensive for low-resource settings or only provide qualitative or semi-quantitative results. GPHF minilab™ is one of them based on thin layer chromatography(TLC) principles with a semi-quantitative capability by visual observation of the spot area and intensity for medicine quality analysis. Thus, its use as a quality control tool for pharmaceutical products has limitations as spot area and intensity visual observation by the naked eye highly varies from analyst to analyst. As such, in this study, the semi-quantitative technique has been transferred to a quantitative approach by capturing the developed TLC plate image using an Android-based mobile phone inside a simple carton box. Then, the spot area was quantified using justTLC software. The quantitative results were compared with the-high performance liquid chromatography (HPLC) method as the golden standard. Accordingly, linearity was observed in the assayed range (80–120% label claim), and the correlation coefficients found were (R2 = 0.958, 0.997, 0.941, and 0.956 for Albendazole, Mebendazole, Artemether, and Lumefantrine, respectively.). The values are satisfactory. The %RSDs found were less than 2% for all drugs [intraday (n = 6) (RSD = 1.17, 1.61, 1.87, and 1.64), and interday (n = 18) (RSD = 1.16, 0.72, 1.12, and 1.18) for Artemether, Lumefantrine, Mebendazole, and Albendazole, respectively]. Moreover, comparisons of results obtained from the sophisticated CAMAG UV cabinet (R2 =0.991, 0.971, 0.946, and 0.967) and the developed simple carton box (R2 = 0.958, 0.997, 0.941, and 0.956) for Albendazole, Mebendazole, Artemether, and Lumefantrine, respectively. The values are comparable and reveal the accuracy of the method. Robustness testings' that were performed under different altered conditions revealed the robustness of the method (RSD less than 2% for all factors). Additionally the deviations from the golden HPLC results were on average −8.62% for albendazole, −3.79% for artemether, and −4.52% for lumefantrine samples. The developed method shows a satisfactory performance capability to utilize the GPHF minilab™ as a quantitative technique for medicine quality control purposes. It will be a very useful tool in a resource-limited setting. The target method profile, which encompasses a simple, low-cost, linear, precise, robust, accurate, and quantitative GPHF minilab™ system, was obtained for Albendazole, Mebendazole, and Arthemeter lumefantine combinations (Co-artem). The proposed method was successfully applied to analyze the content of the marketed medicines in the above mentioned tablets and offered acceptable deviations from the golden HPLC method. Automation of quantitative GPHF minilab™ was highly recommended to enhance the appropriateness and use of this system.

Generation of tunable terahertz pulse carrying orbital angular momentum in non-uniform vortex plasma channel

An amplitude modulated Laguerre-Gaussian (LG) laser beam carrying orbital angular momentum (OAM) is considered for terahertz radiation using non-uniform plasma vortex channel under relativistic conditions. The suggested approach involves the exchange of angular momentum between a non-uniform vortex plasma and a laser beam. During the interaction of non-uniform vortex plasma with photons, the laser angular momentum changes and twisted terahertz radiation is generated. The resultant THz radiation is shown to be substantially dependent on the beam width parameter and non-uniformity in the plasma channel. The amplitude of THz increases with beam focusing and the orbital angular momentum parameter. Due to higher amplitude of THz this study is useful in THz applications like, detection of counterfeit drugs, explosive material, analyze and identify defects in materials, medical imaging and communication.

Spectrophotometric studies of low-cost method for determination of ceftriaxone using a novel charge transfer acceptor, N-(2,4-dinitro-1-naphthyl)-p-toluenesulphonamide

BackgroundThis study reports a new, cost-effective and validated method for the determination of ceftriaxone (CFR). The method involved charge transfer (CT) complexation reaction of ceftriaxone (as n-electron donor) and N-(2,4-dinitro-1-naphthyl)-p-toluenesulphonamide {N-(2,4-DN1NL) PTS} as π-electron acceptor to form a complex. Ultraviolet, infrared and 1H NMR spectra of CFR, N-(2,4-DN1NL) PTS and adduct were then studied to predict the site of interaction between the donor and acceptor.ResultThe complex formed had deep golden-yellow colour, having a new absorption band at 440 nm. Molar absorptivity of 1.667 × 105 L M−1 cm−1 was obtained. The complexation reaction was completed at 30 °C optimal temperature within 10 min. Acetonitrile was found to be the best diluting solvent for optimal detector response and the complex was stable (absorbance unchanged) at room temperature for hours. At concentration of 1.708–11.956 µg mL−1, with low limits of detection of 0.143 µg mL−1, Beer’s law was observed. Between-day recovery statistics of CFR from quality control samples were 102.15 ± 0.062 (% RSD = 0.61, n = 12) over three days. The site of interaction of donor and acceptor molecules, as revealed through infrared (IR) and proton nuclear magnetic resonance studies (1H NMR) and the formation of charge transfer complex is through intermolecular hydrogen bonding between the amino group of the donor and the acidic proton of the acceptor. Common tablet excipients, as observed, did not interfere with the analytical method and no significant difference existed between the results of this new method and the high performance liquid chromatographic procedures (p > 0.05) documented in the USP. The new CT procedure described in this paper is not only simple but also fast, accurate and precise. Also, the reactions were carried out at room temperature compared to previously described procedures.ConclusionsThis novel method could therefore be adopted as a fast but cost-effective alternative for the qualitative and quantitative assessment of CFR in its pure and dosage form. It could find usefulness in on-the-spot detection of counterfeit drugs and in field inspections with reliable accurate results that compares with established methods.

Microwave Cavity Perturbation With 3-D Printed Sample Holders for Detection of Counterfeit Drugs

Microwave Cavity Perturbation With 3-D Printed Sample Holders for Detection of Counterfeit Drugs

DoE Screening and Optimization of Liquid Chromatographic Determination of Nicotinic Acid and Six Statins: Application to Pharmaceutical Preparations and Counterfeit Detection.

An isocratic reversed-phase high performance liquid chromatographic method has been developed and validated to simultaneously determine nicotinic acid, pravastatin sodium, rosuvastatin calcium, atorvastatin calcium, pitavastatin calcium, lovastatin sodium and simvastatin sodium in focus on counterfeit drug detection. Thin-layer chromatography, nuclear magnetic resonance and mass spectrometry have been additionally performed to verify the identification of adulterants of counterfeit herbal medicines. Chromatographic separation was carried out on Inertsil® ODS-3 C18 (4.6 × 150mm, 5μm) with isocratic mobile phase elution containing a mixture of acetonitrile: methanol: 25mM potassium dihydrogen phosphate buffer, pH2.86 adjusted with 0.1M o-phosphoric acid (48: 30: 22, v/v/v), at a flow rate of 1mL/min and with UV detection at 238nm. The design of experiment methodology, Plackett-Burman and Box-Behnken designs, was used to screen and optimize the mobile phase composition. The validation of the method was also carried out under the International Conference on Harmonization guidelines. The developed method was sensitive, accurate, simple, economical and highly robust, in addition to the comprehensiveness and novelty of this method for separating the seven drugs. The results were statistically compared with the reference methods used Student's t-test and variance ratio F-test at P < 0.05.

MULTISENSORY COLORIMETRIC ANALYSIS OF DRUGS DYDROGESTERONE, TROXERUTIN AND ADEMETIONINE USING BARCODES

The aim of this study is to develop a universal, rapid and affordable method for the identification of dydrogesterone, troxerutin, and ademetionine in drugs by multisensor digital colorimetry using a unique two-dimensional code. The developed approach can be applied to rapid detection of counterfeit drugs at the preliminary stage of the analysis (before using more expensive specialized equipment). Materials and methods. To implement the proposed approach, the substances of dydrogesterone (“Abbott Biologicals B.V.”, Netherlands), troxerutin (JSC “Interfarma”, Prague, Czech Republic) and ademetionine (LLC “Farmamed”, Moscow, Russia) , troxerutin capsules 300 mg (LLC “Pranafarm”, Samara, Russia), lyophilisate for an intravenous solution and the intramuscular administration “Heptral” ® (ademetionine) 400 mg (“Abbott Laboratories”, GMBH, Germany), tablets “Duphaston” ® (dydrogesterone) 10 mg (“Abbott Healthcare Products B.V.”, Netherlands), were used. A multisensor colorimetry method has been implemented using the following set of 8 sensors (C 1 -C 8 ): an intact solution – a 96% (v/v) aqueous ethanol solution – C 1 ; 1 mM alcoholic solution of anthraquinone green (CAS#4403-90-1) – C 2 ; a 0.2% aqueous solution of 3-methylbenzothiazolinone hydrazone (CAS#1128-67-2) – C 3 ; a 0.2% methyl orange aqueous solution (CAS#547-58-0) – C 4 ; a 1 mM alcoholic solution of sulforhodamine B (CAS#3520-42-1) – C 5 ; a 1 mM alcoholic solution of 1-hydroxypyrene (CAS#5315-79-7) – C 6 ; 1 mM alcoholic solution of allura red AC (CAS#25956-17-6) – C 7 ; a 1 mM aqueous solution of iron (III) chloride – C 8 . Transparent flat-bottomed polypropylene plates with 96 cells, with a cell volume of 350 µl (Thermo Fischer Scientific, USA, cat. No. 430341) were used as a base for the chip. For obtaining raster images, an Epson Perfection 1670 office flatbed scanner (CCD-matrix) with a removable cover was used. The obtained digital images of the cells were processed using the ImageJ software (Wayne Rasband, National Institutes of Health, USA; http://imagej.nih.gov/ij) with a 24-bit RGB color model (8 bits per channel). Results. The adequacy of the developed approach was confirmed by the analysis of the above-listed drugs. It has been shown that the results obtained have no statistically significant differences from the values determined by the spectrophotometric method. Conclusion. The possibility of using multisensor digital colorimetry for pharmaceutical analysis has been shown. The developed methods for the identification of the active substances can serve as a good supplement to the more expensive traditional methods.

Raman spectroscopy and hierarchical cluster analysis for the ingredients characterization in different formulations of paracetamol and counterfeit paracetamol

The distribution of pharmaceutical ingredients in tablet influences its effectiveness. Direct analysis of tablet using Raman spectroscopy generates information on internal distribution of tablet ingredients. Raman spectra of local and imported formulations of paracetamol clearly discriminated signatures of paracetamol and caffeine in Panadol and Panadol Extra respectively in intact, sliced and powdered tablets/caplets. The presence of few excipients like titanium dioxide in surface coating and calcium carbonate was also detectable in imported Panadol Advance and Panadol Extra caplets with Optizorb® technology which helps in quick disintegration of tablet inside body. Moreover, locally available counterfeit paracetamol was also analysed that showed less intense peaks for active ingredient i.e. paracetamol and few enhanced peaks for excipients as separated by hierarchical cluster analysis (HCA). It is suggested that Raman spectroscopy alongwith chemometrics can be effectively used for the rapid identification and distribution of active drug ingredients in tablets for quality control and detection of counterfeit drugs.

RP-LC Method for the Determination of Seven Antiviral Drugs and Bioanalytical Application for Simultaneous Determination of Lamivudine and Penciclovir in Human Plasma

An RP-LC method was developed and validated for separation and determination of seven antiviral drugs in their drug substances and drug products, using a BDS Hypersil C8 column at ambient temperature. The mobile phase was composed of 0.01 M KH2PO4 (pH 4):acetonitrile in gradient mode and the quantification was achieved at 245 nm for acyclovir, ganciclovir, penciclovir and valacyclovir hydrochloride, and at 220 nm for lamivudine, oseltamivir phosphate and ribavirin. Run time was 8 min, except for the oseltamivir-containing mixture where the run time was extended to 20 min. The validation of the method was assessed according to ICH guidelines. Linearity, accuracy and precision were satisfactory over the concentration ranges 3–100 µg mL−1 for acyclovir, ganciclovir and penciclovir; 5–100, 4–100, 7–120 and 5–120 µg mL−1 for valaciclovir HCl, lamivudine, oseltamivir phosphate and ribavirin, respectively. The developed method is suitable for the quality control and routine analysis of the cited drugs separately or in combinations. Moreover, the proposed method can be used for counterfeit drug detection. Also, simultaneous determination of lamivudine and penciclovir in spiked human plasma has been developed, using valaciclovir hydrochloride as an internal standard. Protein precipitation using perchloric acid solution was used for the extraction of the drugs from plasma. With modified chromatographic conditions, quantification was achieved at 254 nm. Validation of the method was performed according to European Medicines Agency guidelines with linearity over the range 0.056–4.0 and 0.14–10.0 μg mL−1 for lamivudine and penciclovir, respectively.

Quantitative bioassay to identify antimicrobial drugs through drug interaction fingerprint analysis

Drug interaction analysis, which reports the extent to which the presence of one drug affects the efficacy of another, is a powerful tool to select potent combinatorial therapies and predict connectivity between cellular components. Combinatorial effects of drug pairs often vary even for drugs with similar mechanism of actions. Therefore, drug interaction fingerprinting may be harnessed to differentiate drug identities. We developed a method to analyze drug interactions for the application of identifying active pharmaceutical ingredients, an essential step to assess drug quality. We developed a novel approach towards the identification of active pharmaceutical ingredients by comparing drug interaction fingerprint similarity metrics such as correlation and Euclidean distance. To expedite this method, we used bioluminescent E. coli in a simplified checkerboard assay to generate unique drug interaction fingerprints of antimicrobial drugs. Of 30 antibiotics studied, 29 could be identified based on their drug interaction fingerprints. We present drug interaction fingerprint analysis as a cheap, sensitive and quantitative method towards substandard and counterfeit drug detection.

Chemometric aided NIR portable instrument for rapid assessment of medicine quality

The progress in instrumentation technology has led to miniaturization of NIR instruments. Fast systems that contain no moving parts were developed to be used in the field, warehouses, drugstores, etc. At the same time, in general these portable/handheld spectrometers have a lower spectral resolution and a narrower spectral region than stationary ones. Vendors of portable instruments supply their equipment with special software for spectra processing, which aims at simplifying the analyst’s work to the highest degree possible. Often such software is not fully capable of solving complex problems. In application to a real-world problem of counterfeit drug detection we demonstrate that even impaired spectral data do carry information sufficient for drug authentication. The chemometrics aided approach helps to extract this information and thus to extend the applicability of miniaturized NIR instruments. MicroPhazir-RX NIR spectrometer is used as an example of a portable instrument. The data driven soft independent modeling of class analogy (DD-SIMCA) method is employed for data processing. A representative set of tablets of a calcium channel blocker from 6 different manufacturers is used to illustrate the proposed approach. It is shown that the DD-SIMCA approach yields a better result than the basic method provided by the instrument vendor.

Development and Applications of Portable Gas Chromatography-Mass Spectrometry for Emergency Responders, the Military, and Law-Enforcement Organizations.

Portable gas chromatography-mass spectrometry (GC-MS) systems are being deployed for field use, and are designed with this goal in mind. Performance characteristics of instruments that are successful in the field are different from those of equivalent technologies that are successful in a laboratory setting. These field-portable systems are extending the capabilities of the field user, providing investigative leads and confirmatory identifications in real time. Many different types of users benefit from the availability of this technology including emergency responders, the military, and law-enforcement organizations. This manuscript describes performance characteristics that are important for field-portable instruments, especially field-portable GC-MS systems, and demonstrates the value of this equipment to the disciplines of explosives investigations, fire investigations, and counterfeit-drug detection. This paper describes the current state of portable GC-MS technology, including a review of the development of portable GC-MS, as well as a demonstration of the value of this capability using different examples.

Detecting Counterfeit Pharmaceuticals through UV Spectrophotometry

Abstract: According to the World Health Organization between 10%-30% of medicines, in Africa, Asia and South America, are counterfeit or sub-standard, affecting the health of millions of people. Currently, there is no effective way to check the quality of a medicine at the point of care, leaving many with treatable diseases at risk. The goal of this study is to identify UV-Vis (240nm - 500nm) absorbance patterns that would indicate if a drug is sub-standard or counterfeit. UV-Vis spectroscopy was selected as the method for testing due to the maturity and availability of the technology. Pure Acetaminophen and Tylenol were used as controls for proof of concept. Samples were prepared by dissolving different combinations of the pure active ingredient and adulterants such as cement, rice flour, vitamin C and lactose in three different types of solvents (H2O, 0.1 M HCl, 0.1 NaOH). Various concentrations (ranging from 0.01mg/ml to 0.04mg/ml) and mixing ratios were analyzed using a UV-Vis Spectrophotometer. It was found that adulterants significantly decrease the absorption of acetaminophen at 245nm by interacting with its benzene ring, while showing a slight increase in other parts of the spectrum. UV-Vis scans show that the amount of change in absorbance at specific wavelengths, coupled with characteristic wavelength shifts produced by different solvents, can be used for detection of counterfeit drugs. The methods presented here could be used for quality control of medicines at or near the point of care in parts of the world at higher risk of encountering defective pharmaceuticals.

Uncovering Counterfeit Viagra and Cialis Using Portable Nir and Uv-Visible Spectroscopy Coupled with Multivariate Data Analysis : A Preliminary Study

In this study, two of the most common drugs (Cialis ® and Viagra ® ) that are subjected to adulteration were investigated. The investigation involved examining the above drugs using both portable NIR and UV-Visible spectroscopy. The obtained spectral data were analyzed using multivariate chemometric methods such as Principal Components Analysis (PCA) and Cluster Analysis (CA). Discriminating between the original and the counterfeit drugs was successfully demonstrated with no or little chemical pretreatment. Detection of counterfeit drugs from different sources was also possible.

Inspection of Solid Dosage Forms using THz Imaging Spectroscopy

Abstract The present work describes a laboratory terahertz (THz) imaging spectroscopy system and its possibilities to inspect solid dosage forms in the form of coated tablets and capsules. Moreover, the chemical composition and layer structure of coated pharmaceutical tablets are investigated. These chemical and physical properties of solid dosage forms can be used for the detection of counterfeit drugs. Preliminary results show that THz time domain spectroscopy and imaging is a promising technology for contactless control and analysis of pharmaceutical drug materials and final dosage forms.

Noninvasive detection of counterfeited ampoules of dexamethasone using NIR with confirmation by HPLC-DAD-MS and CE-UV methods

Application of near-infrared (NIR) measurements together with chemometric data processing is widely used for counterfeit drug detection. The most difficult counterfeits to detect are the "high quality fakes", which have the proper composition but are produced in violation of technological regulations by underground manufacturers. This study uses such forgeries and addresses important issues. The first is the possibility of applying the NIR/chemometric approach to the detection of injectable formulations of drugs (in this case dexamethasone), which are aqueous solutions with low concentration of active ingredients, directly in the closed ampoules. The second issue is the comparison of NIR/chemometric conclusions with detailed chemical analysis.

Whispering-gallery-mode resonance sensor for dielectric sensing of drug tablets

We propose, for the first time, the application of whispering gallery mode (WGM) perturbation technique in dielectric analysis of disk shape pharmaceutical tablets. Based on WGM resonance, a low-cost high sensitivity sensor in milllimeter-wave frequency range is presented. A comprehensive sensitivity analysis was performed to show that a change in the order of 10−4 in the sample permittivity can be detected by the proposed sensor. The results of various experiments carried out on drug tablets are reported to demonstrate the potential multifunctional capabilities of the sensor in moisture sensing, counterfeit drug detection and contamination screening. Analytically, two sample placement configurations, i.e. a tablet placed on top of a dielectric disk resonator and inside a dielectric ring resonator, have been studied to predict the resonance frequency and Q-factor of the combined sample-resonator structure. The accuracy of the analytical model was tested against full-wave simulations and experimental data.

Roles for pharmacy in combatting counterfeit drugs

Objectives:To describe (1) the international scope of counterfeit drugs, (2) international and U.S. anticounterfeiting initiatives, and (3) the enhanced roles and challenges facing pharmaceutical organizations and individual pharmacists to thwart counterfeit drugs. Data sources:PubMed and Ovid from 1970 to 2008 using the search terms counterfeit drugs, counterfeit pharmaceuticals, and counterfeit medicines, with English as the limiting term. Nonprimary literature sources included the U.S. Food and Drug Administration (FDA) Web site (www.fda.gov) from 1990 to 2008 using the search term counterfeit drugs, presentations from meetings or workshops attended or accessed via the Internet, and Web sites of professional organizations. Additional resources were identified from personal bibliographies collected by the author and bibliographies of gathered articles. Data synthesis:Counterfeit drugs—defined as those containing no active ingredient, an incorrect amount of active ingredients, incorrect ingredient, and/or unapproved labeling and packaging—represent an unquantified problem of international proportions. The existing situation has been facilitated by inconsistent national regulatory oversight, disparate unlinked databases, lack of unified anticounterfeiting actions, and inability to track the distribution of domestically produced or imported drug products between, among, and within nations. In the United States, several important anticounterfeiting initiatives announced by FDA in 2004 have been implemented but the benefits of others, such as electronic tracking of a drug's movement through the U.S. distribution chain to a dispensing pharmacy, will not be realized in the near future. The role of pharmacists as patient educators, prudent purchasers, and detectors of counterfeit drugs can typically be accomplished with minimal added expense or work; however, the impact of electronic tracking on pharmacies' expenses and workflow is unknown. Pharmacists need to be included in efforts to thwart receipt of counterfeit drugs by patients, but this must be accomplished with minimal negative impact on pharmacy practices. Conclusion:Although consistent detection of counterfeit drugs is difficult, pharmacists can take several reasonable measures to lessen the chances they are dispensing counterfeit drugs. However, the increased role of pharmacists is accompanied by several important challenges involving increased expense and altered business practices.

Emerging Non-invasive Raman Methods in Process Control and Forensic Applications

This article reviews emerging Raman techniques (Spatially Offset and Transmission Raman Spectroscopy) for non-invasive, sub-surface probing in process control and forensic applications. New capabilities offered by these methods are discussed and several application examples are given including the non-invasive detection of counterfeit drugs through blister packs and opaque plastic bottles and the rapid quantitative analysis of the bulk content of pharmaceutical tablets and capsules without sub-sampling.

Establishment of an HPLC identification system for detection of counterfeit steroidal drugs

A set of simple HPLC methods employing UV detection were developed for detection of counterfeit drugs by the qualitative and quantitative analysis of nine steroidal drugs, ethinylestradiol, diethylstilbestrol, norethisterone, norgestrel, methyltestosterone, medroxyprogesterone acetate, progesterone, testosterone propionate and nilestriol. The methods were based on studies of the relationships between the retention factors ( k) of the nine compounds and the percentages of water to methanol in the mobile phases on a reverse phase Alltima C 18 column giving reliable separation of the compounds under three sets of chromatographic conditions. The methods were validated using statistical tests and were used on nine commercial samples for detection of possible counterfeit drugs.

NIR spectrometry for counterfeit drug detection: A feasibility study

Express-methods for detection of counterfeit drugs are of vital necessity. Visual control, dissociating tests or simple color reaction tests reveal only very rough forgeries. The feasibility of information-rich NIR-measurements as an analytical method together with multivariate calibration for mathematical data processing for false drugs detection is demonstrated. Also, multivariate hyperspectral image analysis is applied providing additional diagnostic information. Hyperspectral imaging is becoming a useful diagnostic tool for identifying non-homogeneous spatial regions of drug formulation. Two types of drugs are used to demonstrate the applicability of these approaches.