Analysis Of Pharmaceutical Formulations Research Articles

Estimation of Piroxicam in Tablet Dosage Form by using UV-Vis. Spectrophotometer

A simple, accurate, sensitive and precise Ultraviolet spectrophotometric method has been developed for the determination of Piroxicam in tablet dosage form. The solutions of standard and sample were prepared in methanol. In the UV specrophotometric method, the quantitative determination of the drug was carried at 335 nm and the linearity range was found to be 2–12 μg/ml. The calibration graphs constructed at their wavelength of determination were found to be linear for specrophotometric methods. The proposed methods have been extensively validated statistically that included parameters such as linearity, accuracy, precision, LOD, LOQ, recovery and robustness. There was no significant difference between the performance of the proposed method regarding the mean values and standard deviations. The described methods can be readily utilized for analysis of pharmaceutical formulation.

Development and Validation of a Sensitive RP-HPLC method for Simultaneous Estimation of Rosuvastatin and Fenofibrate in Tablet Dosage form by using PDA Detector in Gradient Mode

Objective: The present work was undertaken with the aim to develop and validate a rapid and consistent RP-HPLC method in which the peaks will be appear with short period of time as per ICH Guidelines. The proposed method was simple, fast, accurate and precise method for the Quantification of drug in the dosage form, bulk drug as well as for routine analysis in Quality control. Method: RP-HPLC method was developed and validated for simultaneous estimation of Rosuvastatin and Fenofibrate in bulk drug and in combined dosage forms. The HPLC separation was achieved on a XTerra C18 (4.6 X 150mm, 5?m, Make: Thermosil) or equivalent in an Isocratic Mode. The mobile phase was composed of Phosphate Buffer (25%) whose pH was adjusted to 3.0 by using Ortho Phosphoric Acid and Methanol (75%) [HPLC Grade] Results: The flow rate was monitored at 1.0ml per min. The wavelength was selected for the detection was 254 nm. The run time was 7min. The retention time found for the drugs Rosuvastatin and Fenofibrate were 1.997 min., 3.238 min. and 4.042 min. respectively. The % recovery was found to be 98.46% - 101.79% for the drug Rosuvastatin. The % recovery was found to be 98.04% - 101.79% for the drug Fenofibrate. The linearity was established in the range of 80 to 120ppm for the drug Rosuvastatin and 2.4 to3.6ppm for the drug Fenofibrate. The LOD for the drugs Rosuvastatin and Fenofibrate were found to be 0.07µg/ml, 0.07µg/ml and 0.006µg/ml respectively. The LOQ for the drugs Rosuvastatin and Fenofibrate were found to be 0.23µg/ml, 0.24µg/ml and 0.02µg/ml respectively. Conclusion: The proposed method was adequate sensitive, reproducible, and specific for the determination of Rosuvastatin and Fenofibrate in bulk as well as in Tablet dosage form. The validation of method was carried out utilizing ICH-guidelines. The described RP-HPLC method was successfully employed for the analysis of pharmaceutical formulations containing combined dosage form. Overall the proposed method was found to be suitable and accurate for the Quantitative determination of the drug in Tablet dosage form. The method was simple, precise, accurate and sensitive and applicable for the simultaneous determination of Rosuvastatin and Fenofibrate in bulk drug and in combined dosage forms.

Hantzsch Reaction as a Method for Spectrofluorimetric Analysis of Penicillin G

A sensitive, selective, and validated spectrofluorimetric method is being described for the determination of penicillin G. The method utilizes this drug (as a source of the amine moiety) to react with acetylacetone and formaldehyde through the Hantzsch reaction. The faint yellow product of dihydropyridine derivatives was measured at an emission wavelength of 481 nm (after excitation at 416 nm). Linear calibration graphs were obtained in the range of 0.2-200 μg/mL. The experimental limits of detection and quantitation were 0.170 and 0.515 μ/mL, respectively. The relative standard deviation (n=5) at the 100 μg/mL level were 6.11 for intra-day precision and 9.42 for inter-day precision. The method was successfully applied in the analysis of pharmaceutical formulation; the recovery was quantitative, and the result obtained agreed with those obtained by another reported method.

Development and Validation of an HPLC Method for Simultaneous Determination of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol Hydrochloride in Pharmaceutical Formulations.

Tuberculosis treatment consists of a fixed dose combination of rifampicin (RIF), isoniazid (INH), pyrazinamide (PYZ), and ethambutol hydrochloride (EMB). The combined treatment using various drugs is necessary for patient curing, without recrudescence, and for prevention of drug-resistant mutants, which may occur during treatment. An HPLC-diode array detector (DAD) method for the simultaneous determination of RIF, INH, PYZ, and EMB in fixed dose combination tablets was developed and validated. Chromatographic experiments were performed on an Agilent 1200 HPLC system, and the separation was carried out on a Purospher STAR RP18e (250×4.6 mm id, 5 μm, Merck) analytical column. Gradient elution was carried out with a mobile phase of 20 mM monobasic sodium phosphate buffer with 0.2% triethylamine (pH 7.0) and acetonitrile at a flow rate of 1.5 mL/min. The total run time was 12 min, and the re-equilibration time was 5 min. EMB detection was performed at 210 nm, and RIF, INH, and PYZ were detected at 238 nm, using a DAD. The method proved to be specific, linear (r2>0.99), precise (RSD<2%), accurate, and robust and may be applied to the QC analysis of pharmaceutical formulations.

Chemometrics resolution and quantification power evaluation: Application on pharmaceutical quaternary mixture of Paracetamol, Guaifenesin, Phenylephrine and p-aminophenol

Three advanced chemmometric-assisted spectrophotometric methods namely; Concentration Residuals Augmented Classical Least Squares (CRACLS), Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Principal Component Analysis-Artificial Neural Networks (PCA-ANN) were developed, validated and benchmarked to PLS calibration; to resolve the severely overlapped spectra and simultaneously determine; Paracetamol (PAR), Guaifenesin (GUA) and Phenylephrine (PHE) in their ternary mixture and in presence of p-aminophenol (AP) the main degradation product and synthesis impurity of Paracetamol. The analytical performance of the proposed methods was described by percentage recoveries, root mean square error of calibration and standard error of prediction. The four multivariate calibration methods could be directly used without any preliminary separation step and successfully applied for pharmaceutical formulation analysis, showing no excipients’ interference.

Matrix Effects in Quantitative Assessment of Pharmaceutical Tablets Using Transmission Raman and Near-Infrared (NIR) Spectroscopy.

Raman spectroscopy can be an alternative to near-infrared spectroscopy (NIR) for nondestructive quantitative analysis of solid pharmaceutical formulations. Compared with NIR spectra, Raman spectra have much better selectivity, but subsampling was always an issue for quantitative assessment. Raman spectroscopy in transmission mode has reduced this issue, since a large volume of the sample is measured in transmission mode. The sample matrix, such as particle size of the drug substance in a tablet, may affect the Raman signal. In this work, matrix effects in transmission NIR and Raman spectroscopy were systematically investigated for a solid pharmaceutical formulation. Tablets were manufactured according to an experimental design, varying the factors particle size of the drug substance (DS), particle size of the filler, compression force, and content of drug substance. All factors were varied at two levels plus a center point, except the drug substance content, which was varied at five levels. Six tablets from each experimental point were measured with transmission NIR and Raman spectroscopy, and their concentration of DS was determined for a third of those tablets. Principal component analysis of NIR and Raman spectra showed that the drug substance content and particle size, the particle size of the filler, and the compression force affected both NIR and Raman spectra. For quantitative assessment, orthogonal partial least squares regression was applied. All factors varied in the experimental design influenced the prediction of the DS content to some extent, both for NIR and Raman spectroscopy, the particle size of the filler having the largest effect. When all matrix variations were included in the multivariate calibrations, however, good predictions of all types of tablets were obtained, both for NIR and Raman spectroscopy. The prediction error using transmission Raman spectroscopy was about 30% lower than that obtained with transmission NIR spectroscopy.

Development and application of graphite-SiO2/Al2O3/Nb2O5-methylene blue (GRP-SiAlNb-MB) composite for electrochemical determination of dopamine

In the present paper an amperometric sensor based on graphite-SiO2/Al2O3/Nb2O5-methylene blue (GRP-SiAlNb-MB) composite has been successfully prepared for dopamine (DA) determination in real samples. The electrochemical behavior of DA at the GRP-SiAlNb-MB has been evaluated by employing cyclic voltammetry. The best ratio (m/m) of GRP-SiAlNb-MB composite was found to be 1:0.54. Under optimized conditions (pH 7.5 in 0.15molL−1 phosphate buffer) the amperometry method responds linearly to DA from 5.0 up to 500.0μmolL−1 (r=0.995) with limits of detection and quantification of 1.49 and 4.97μmolL−1, respectively. The developed method was successfully applied for DA determination in real samples of pharmaceutical formulations and can be used for routine quality control analysis of pharmaceutical formulations containing DA. The use of inorganic matrix SiAlNb was found to be very useful to adsorb MB in the composite material with further improvement of the anodic peak current of DA.

QBD BASED RP-HPLC METHOD FOR SCREENING AND ANALYSIS OF TELAPRAVIR AND 7 OTHER ANTIRETROVIRAL AGENTS

The present study describes the separation and simultaneous estimation of eight anti-retroviral drugs, namely, Telaprevir (TPV), Emtricitabine (ECB), Fosamprenavir (FANV), Tenofavir (TNF), Ritonavir (RNV), Raltegravir (RGV) and Oseltamivir (OSMV) and Zidovudine (ZDV) as an active pharmaceutical ingredient, by RP-HPLC method by applying the principles of Quality by Design (QbD). An application of DoE (Design of Experiments) full factorial design was used for initial screening and optimization. The final optimized method consists of separation being carried out on a Fortis C18 column (150 mm × 4.6 mm, 5μ particle size) using acetonitrile and 10 mm ammonium formate buffer (pH 3 adjusted with formic acid) using a gradient program. The quantitative evaluation was performed with a diode array detector at 251 nm and 230 nm with a flow rate of 1 mL min–1. Suitability of this method for the quantitative determination of the drugs was proved by validation in accordance with the International Conference on Harmonization (ICH) guidelines. The method is selective, precise, robust and accurate and can be used for routine analysis of pharmaceutical formulations in quality control and counterfeit screening.

A validated high-performance thin-layer chromatographic method for the assay of two binary mixtures containing omeprazole or its isomer esomeprazole in pharmaceutical dosage forms

A simple validated high-performance thin-layer chromatographic (HPTLC) method was developed for the determination of two binary mixtures containing omeprazole with ketoprofen (mixture 1) and esomeprazole with naproxen (mixture 2). The separation was carried out on Merck HPTLC aluminum plates precoated with silica gel 60 F254 (20 × 10 cm) with 250-μm thickness using chloroform-ethyl acetate (3:7, v/v) as the mobile phase. HPTLC separation of the four drugs in the two binary mixtures, followed by densitometric measurement, was carried out in the absorbance mode at 302 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r > 0.999 in the concentration ranges of 0.03–0.3 μg band−1 for omeprazole (OME) and esomeprazole (ESO), 0.2–2 μg band−1 for ketoprofen (KETO), and 0.5–6 μg band−1 for naproxen (NAP). The proposed method was validated and successfully applied for the analysis of pharmaceutical formulations and synthetic mixtures containing the two combination...

Novel spectrophotometric methods for simultaneous determination of Amlodipine, Valsartan and Hydrochlorothiazide in their ternary mixture

This work represents a comparative study of two smart spectrophotometric techniques namely; successive resolution and progressive resolution for the simultaneous determination of ternary mixtures of Amlodipine (AML), Hydrochlorothiazide (HCT) and Valsartan (VAL) without prior separation steps. These techniques consist of several consecutive steps utilizing zero and/or ratio and/or derivative spectra. By applying successive spectrum subtraction coupled with constant multiplication method, the proposed drugs were obtained in their zero order absorption spectra and determined at their maxima 237.6nm, 270.5nm and 250nm for AML, HCT and VAL, respectively; while by applying successive derivative subtraction they were obtained in their first derivative spectra and determined at P230.8–246, P261.4–278.2, P233.7–246.8 for AML, HCT and VAL respectively. While in the progressive resolution, the concentrations of the components were determined progressively from the same zero order absorption spectrum using absorbance subtraction coupled with absorptivity factor methods or from the same ratio spectrum using only one divisor via amplitude modulation method can be used for the determination of ternary mixtures using only one divisor where the concentrations of the components are determined progressively. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulation containing the cited drugs. Moreover comparative study between spectrum addition technique as a novel enrichment technique and a well established one namely spiking technique was adopted for the analysis of pharmaceutical formulations containing low concentration of AML. The methods were validated as per ICH guidelines where accuracy, precision and specificity were found to be within their acceptable limits. The results obtained from the proposed methods were statistically compared with the reported one where no significant difference was observed.

Analytical Method Development and Validation for the Determination of Allopurinol and Alphalipoic Acid Using Reverse Phase HPLC Method in Bulk and Tablet Dosage Form

A new simple, accurate, precise and reproducible RP-HPLC method has been developed for the simultaneous estimation of Allopurinol and Alpha lipoic acid in bulk and pharmaceutical dosage form using C18 column (inertsil ODS, 250 x 4.6 mm, 5 μm) in isocratic mode. The mobile phase consisted of 0.1 M Dipotassium Phosphate buffer (pH 3.5) and acetonitrile in the ratio of 55:45v/v. The detection was carried out at 250 nm for Allopurinol and 212 nm for Alpha lipoic acid. The method was linear over the concentration range for Allopurinol 60–140 μg/ml and for Alpha lipoic acid 60–140μg/ml. The recoveries of Allopurinol and Alpha lipoic acid were found to be 98.9% and 98.7% respectively. The validation of method was carried out utilizing ICH-guidelines. The described HPLC method was successfully employed for the analysis of pharmaceutical formulations containing combined dosage form.

A comparative study of novel spectrophotometric resolution techniques applied for pharmaceutical mixtures with partially or severely overlapped spectra

Simultaneous determination of mixtures of lidocaine hydrochloride (LH), flucortolone pivalate (FCP), in presence of chlorquinaldol (CQ) without prior separation steps was applied using either successive or progressive resolution techniques. According to the concentration of CQ the extent of overlapping changed so it can be eliminated from the mixture to get the binary mixture of LH and FCP using ratio subtraction method for partially overlapped spectra or constant value via amplitude difference followed by ratio subtraction or constant center followed by spectrum subtraction spectrum subtraction for severely overlapped spectra. Successive ratio subtraction was coupled with extended ratio subtraction, constant multiplication, derivative subtraction coupled constant multiplication, and spectrum subtraction can be applied for the analysis of partially overlapped spectra. On the other hand severely overlapped spectra can be analyzed by constant center and the novel methods namely differential dual wavelength (D1 DWL) for CQ, ratio difference and differential derivative ratio (D1 DR) for FCP, while LH was determined by applying constant value via amplitude difference followed by successive ratio subtraction, and successive derivative subtraction. The spectra of the cited drugs can be resolved and their concentrations are determined progressively from the same ratio spectrum using amplitude modulation method. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures and were successfully applied for the analysis of pharmaceutical formulations containing the cited drugs with no interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with those of the official or reported methods; using student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision.

A comparative study of different aspects of manipulating ratio spectra applied for ternary mixtures: Derivative spectrophotometry versus wavelet transform

This work represents a comparative study of different aspects of manipulating ratio spectra, which are: double divisor ratio spectra derivative (DR-DD), area under curve of derivative ratio (DR-AUC) and its novel approach, namely area under the curve correction method (AUCCM) applied for overlapped spectra; successive derivative of ratio spectra (SDR) and continuous wavelet transform (CWT) methods. The proposed methods represent different aspects of manipulating ratio spectra of the ternary mixture of Ofloxacin (OFX), Prednisolone acetate (PA) and Tetryzoline HCl (TZH) combined in eye drops in the presence of benzalkonium chloride as a preservative. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulation containing the cited drugs. The proposed methods were validated according to the ICH guidelines. A comparative study was conducted between those methods regarding simplicity, limitation and sensitivity. The obtained results were statistically compared with those obtained from the reported HPLC method, showing no significant difference with respect to accuracy and precision.

Direct analysis in real time – High resolution mass spectrometry as a valuable tool for the pharmaceutical drug development

In this study, direct analysis in real time-mass spectrometry (DART-MS) was assessed for the analysis of various pharmaceutical formulations with intention to summarize possible applications for the routine pharmaceutical development. As DART is an ambient ionization technique, it allows direct analysis of pharmaceutical samples in solid or liquid form without complex sample preparation, which is often the most time-consuming part of the analytical method. This makes the technique suitable for many application fields, including pharmaceutical drug development. DART mass spectra of more than twenty selected tablets and other common pharmaceutical formulations, i.e. injection solutions, ointments and suppositories developed in the pharmaceutical industry during several recent years are presented. Moreover, as thin-layer chromatography (TLC) is still very popular for the monitoring of the reactions in the synthetic chemistry, several substances were analyzed directly from the TLC plates to demonstrate the simplicity of the technique. Pure substance solutions were spotted onto a TLC plate and then analyzed with DART without separation. This was the first DART-MS study of pharmaceutical dosage forms using DART–Orbitrap combination. The duration of sample analysis by the DART-MS technique lasted several seconds, allowing enough time to collect sufficient number of data points for compound identification. The experimental setup provided excellent mass accuracy and high resolution of the mass spectra which allowed unambiguous identification of the compounds of interest. Finally, DART mass spectrometry was also used for the monitoring of the selected impurity distribution in the atorvastatin tablets. These measurements demonstrated DART to be robust ionization technique, which provided easy-to-interpret mass spectra for the broad range of compounds. DART has high-throughput potential for various types of pharmaceutical analyses and therefore eliminates the time for sample cleanup and chromatographic separation.

Method transfer in the bioanalytical laboratory.

Scope & terminology This article covers the principles involved in transferring bioanalytical methods used to determine the pharmacokinetics of dosed drugs. It is not an attempt to discuss the technologies and processes involved in transferring methods used to characterize and/or monitor the stability of formulated products. It does, however, reference the progress in this area where it is felt there may be lessons to be learnt from the GMP process. In view of the lack of a regulatory guidance relevant to bioanalytical methods, it draws heavily on the principals involved in the transfer of such methods. It is the objective of this article to initiate a discussion on the principles involved in the transfer of a wide range of methods covering a range of technologies used to quantify both small new chemical entities and macromolecules. The terminology used is that proposed by the International Society for Pharmaceutical Engineers (ISPE) [1] and the United States Pharmacopeia (USP) [2]. In the GMP pharmaceutical formulation analysis arena, there is one document that has become the de facto reference standard for technology transfer and analytical methodology. This is the ‘Technical Transfer Guide’ produced by the ISPE, which uses the terms ‘receiving’ and ‘sending’ laboratory. A recent USP document uses similar terminology to the ISPE [2]. Although these terms have by no means been mandated, they have gained wide acceptance in GMP formulation analysis. Both papers use the term ‘sending laboratory’ to identify the laboratory that generates the methodology, while the receiving laboratory is the one that will implement the methodology. The validation criteria used are those defined in the US FDA and EMA bioanalytical methods guidances [3,4]. No reference has been made to the 2013 draft FDA document [5], which was published during the writing of this article, as any attempts to pre-empt conclusions drawn from that paper may confuse the situation.

A comparative study of progressive versus successive spectrophotometric resolution techniques applied for pharmaceutical ternary mixtures

This work represents a comparative study of a novel progressive spectrophotometric resolution technique namely, amplitude center method (ACM), versus the well-established successive spectrophotometric resolution techniques namely; successive derivative subtraction (SDS); successive derivative of ratio spectra (SDR) and mean centering of ratio spectra (MCR). All the proposed spectrophotometric techniques consist of several consecutive steps utilizing ratio and/or derivative spectra. The novel amplitude center method (ACM) can be used for the determination of ternary mixtures using single divisor where the concentrations of the components are determined through progressive manipulation performed on the same ratio spectrum. Those methods were applied for the analysis of the ternary mixture of chloramphenicol (CHL), dexamethasone sodium phosphate (DXM) and tetryzoline hydrochloride (TZH) in eye drops in the presence of benzalkonium chloride as a preservative. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulation containing the cited drugs. The proposed methods were validated according to the ICH guidelines. A comparative study was conducted between those methods regarding simplicity, limitation and sensitivity. The obtained results were statistically compared with those obtained from the official BP methods, showing no significant difference with respect to accuracy and precision.

A NEW AND RAPID ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF METFORMIN, PIOGLITAZONE AND GLIMEPRIDE IN TABLET DOSAGE FORM BY USING UPLC

The present work was undertaken with the aim to develop and validate a rapid and consistent UPLC method in which the peaks will be appear with short period of time as per ICH Guidelines. The proposed method was simple, fast, accurate and precise method for the Quantificatio n of drug in the dosage form, bulk drug as well as for routine analysis in Quality control. U PL C method was developed and validated for simultaneous estimation of Metformin, Pioglitazone and Glimepiride in bulk drug and in combined dosage forms. The UPLC separation was achieved on a Symmetry C 18 (2.1 x 100 mm, 1.7 μ m, Make: BEH) or equivalent in an Isocratic Mode. The mobile phase was composed of Phosphate Buffer (25 %) whose pH was adjusted to 4.3 by using Ortho Phosphoric Acid and Methanol (75 %) [UPLC Grade] The flow rate was monitored at 0.25 ml per min. The wavelength was selected for the detect ion was 258 nm. The run time was 5 min utes . The retention time found for the drugs Metformin, Pioglitazone and Glimepiride were 0 .002 minutes , 1.773 min utes and 2.409 minutes respectively. The % recovery was found to be 99.7 % - 100.9 % for the drug Metfor min. The % recovery was found to be 98.4 % - 100.9 % for the drug Pioglitazone. The % recovery was found to be 99.9 % - 101.2 % for the drug Glimepiride. The linearity was established in the range of 400 to 600 ppm for the drug Metformin and 12 to18 ppm fo r the drug Pioglitazone and 0.8 to 1.2 ppm for the drug Glimepiride. The LOD for the drugs Metformin, Pioglitazone and Glimepiride were found to be 0.12 µg/ml , 0.002 µg/ml and 0.002 µg/ml respectively. The LOQ for the drugs Metformin, Pioglitazone and Glim epiride were found to be 0.45 µg/ml , 0.15 µg/ml and 0.08 µg/ml respectively. The proposed method was adequate sensitive, reproducible, and specific for the determination of Metformin, Pioglitazone and Glimepiride in bulk as well as in Tablet dosage form. T he validation of method was carried out utilizing ICH - guidelines. The described UPLC method was successfully employed for the analysis of pharmaceutical formulations containing co mbined dosage form. Overall the proposed method was found to be suitable and accurate for the Quantitative determination of the drug in Tablet dosage form. The method was simple, precise, accurate and sensitive and applicable for the simultaneous determination of Metformin, Pioglitazone and Glim epiride in bulk drug and in

A highly improved method for sensitive determination of amitriptyline in pharmaceutical formulations using an unmodified carbon nanotube electrode in the presence of sulfuric acid

The present paper describes a novel, simple and reliable differential pulse voltammetric method for determining amitriptyline (AMT) in pharmaceutical formulations. It has been described for many authors that this antidepressant is electrochemically inactive at carbon electrodes. However, the procedure proposed herein consisted in electrochemically oxidizing AMT at an unmodified carbon nanotube paste electrode in the presence of 0.1molL−1 sulfuric acid used as electrolyte. At such concentration, the acid facilitated the AMT electroxidation through one-electron transfer at 1.33V vs. Ag/AgCl, as observed by the augmentation of peak current. Concerning optimized conditions (modulation time 5ms, scan rate 90mVs−1, and pulse amplitude 120mV) a linear calibration curve was constructed in the range of 0.0–30.0μmolL−1, with a correlation coefficient of 0.9991 and a limit of detection of 1.61μmolL−1. The procedure was successfully validated for intra- and inter-day precision and accuracy. Moreover, its feasibility was assessed through analysis of commercial pharmaceutical formulations and it has been compared to the UV–vis spectrophotometric method used as standard analytical technique recommended by the Brazilian Pharmacopoeia.

Technologies for detecting falsified and substandard drugs in low and middle-income countries.

Falsified and substandard drugs are a global health problem, particularly in low- and middle-income countries (LMIC) that have weak pharmacovigilance and drug regulatory systems. Poor quality medicines have important health consequences, including the potential for treatment failure, development of antimicrobial resistance, and serious adverse drug reactions, increasing healthcare costs and undermining the public's confidence in healthcare systems. This article presents a review of the methods employed for the analysis of pharmaceutical formulations. Technologies for detecting substandard and falsified drugs were identified primarily through literature reviews. Key-informant interviews with experts augmented our methods when warranted. In order to aid comparisons, technologies were assigned a suitability score for use in LMIC ranging from 0–8. Scores measured the need for electricity, need for sample preparation, need for reagents, portability, level of training required, and speed of analysis. Technologies with higher scores were deemed the most feasible in LMICs. We categorized technologies that cost $10,000 USD or less as low cost, $10,000–100,000 USD as medium cost and those greater than $100,000 USD as high cost technologies (all prices are 2013 USD). This search strategy yielded information on 42 unique technologies. Five technologies were deemed both low cost and had feasibility scores between 6–8, and an additional four technologies had medium cost and high feasibility. Twelve technologies were deemed portable and therefore could be used in the field. Many technologies can aid in the detection of substandard and falsified drugs that vary from the simplest of checklists for packaging to the most complex mass spectrometry analyses. Although there is no single technology that can serve all the requirements of detecting falsified and substandard drugs, there is an opportunity to bifurcate the technologies into specific niches to address specific sections within the workflow process of detecting products.

Chemiluminometric determination of ascorbic acid in pharmaceutical formulations exploiting photo‐activation of GSH‐capped CdTe quantum dots

An automated multi-pumping flow system is proposed for the chemiluminometric determination of ascorbic acid in pharmaceutical formulations, relying on the ability of semiconductor nanocrystals to generate short-lived reactive species upon photo-irradiation. A photo-unit based on visible-light-emitting diodes is used to photo-excite cadmium telluride (CdTe) quantum dots capped with glutathione, leading to the generation of radicals that react with luminol under alkaline conditions, yielding the chemiluminescence. Ascorbic acid acts as a radical scavenger, preventing the oxidation of luminol, thus ensuring a concentration-dependent chemiluminescence quenching. After system optimization, a linear working range of 5.0 × 10(-7) to 5.0 × 10(-6) mol/L ascorbic acid (r = 0.9967, n = 5) was attained, with a detection limit of 3.05 × 10(-7) mol/L and a sampling rate of 200/h. The flow system was applied to the analysis of pharmaceutical formulations and the results were in good agreement with those obtained by the reference titrimetric procedure (RD < ± 4.3%, n = 7).