Melanochrome-based colorimetric assay for quantitative detection of levodopa in co-presence of carbidopa and its application to relevant anti-Parkinson drugs.

In this paper is reported the selective detection and quantification of levodopa in co-presence of carbidopa. The method took advantage of the spontaneous oxidation and color development of levodopa at basic pH here driven by alkaline earth cations and co-solvent in solution. We have shown for the first time the generation and stabilization of the purple melanochrome from levodopa, by using magnesium acetate and dimethyl sulfoxide, which was here exploited for the development of a quantitative colorimetric assay for the active principle ingredient in commercial drugs for the treatment of Parkinson's disease. The calibration curves of levodopa in the two tablet formulations, containing carbidopa as decarboxylase inhibitor, showed a common linear trend between 10 mg L-1 and 40 mg L-1 with levodopa alone or in combination with carbidopa in standard solutions, with very good reproducibility (CVav%, 3.3% for both brand and generic drug) and very good sensitivity, with limit of quantification about 0.6 mg L-1 in any case. The colorimetric method here developed is very simple and effective, appearing as a rapid and low-cost alternative to other methodologies, involving large and expensive instrumentations, for drug estimation and quality control of pharmaceutical formulations.

Differential coulometry based on dual screen-printed strips for high accuracy levodopa determination towards Parkinson's disease management.

As a vital therapeutic agent for Parkinson's disease, dosage control of levodopa has always been a major obstacle in ensuring efficacy and curbing side effects. Simple and fast electrochemical detection methods are the main force in this field. Here, we presented a differential dual-strip method based on the coulometry for high accuracy determination of levodopa. The difference between the two strip signals with or without the tyrosinase extracted the levodopa signal from the samples. The Prussian Blue modified carbon screen-printed electrode was used to convert and amplify the electrochemical signal upon the presence of levodopa. The system exhibited a linear behavior in the 0-10 µM concentration range and a detection limit of 0.25 µM. Furthermore, it was proved to be stable in effectively distinguishing levodopa from complex samples through anti-interference experiments and serum tests. We demonstrated the superiority of dual-strip differential coulometry for the determination of levodopa towards Parkinson's disease clinical management.

The convenient use of fluorescamine for spectrofluorimetric quantitation of pramipexole in pure form and pharmaceutical formulation; application to content uniformity testing.

Pramipexole is a selective dopamine receptor agonist which is used in the treatment of Parkinson's disease and restless legs syndrome. The present work illustrates the development and validation of a sensitive and selective spectrofluorometric method for quantitation of pramipexole (PMP) through its interaction with fluorescamine at pH 7.5 using aqueous borate buffer to produce a highly fluorescent product. The fluorescent intensity of the formed product was measured at 480 nm after excitation at 391 nm. Experimental factors that could influence the formation, stability and the fluorescence intensity of the formed product were investigated and optimized. The linearity of the proposed method was achieved in the concentration range of 0.05-2.0 µg/mL. The quantitation and detection limits were 47 and 15 ng/mL, respectively. The proposed method has been validated in respect to guidelines of ICH and pharmaceutical tablets of PMP were successfully analyzed. Moreover, the method was applied for studying the content uniformity test according to the guidelines of United States Pharmacopeia.

Determining the Distribution of Active Pharmaceutical Ingredients in Combination Tablets Using Near IR and Low-Frequency Raman Spectroscopy Imaging.

Combination tablets containing multiple active pharmaceutical ingredients (APIs) are expected to improve patient convenience by decreasing the number of tablets to be taken; thus, numerous formulations containing multiple APIs have recently been developed. To allow for dose adjustments based on patient conditions, many tablets have a bisection line to allow equal division of tablets. However, there have been no investigations regarding content uniformity among divided combination tablets. Therefore, in this study, the content uniformity of combination tablets after division was investigated using near IR and low-frequency (LF) Raman spectroscopy imaging as well as the Japanese Pharmacopoeia (JP) content uniformity tests. As model drugs, five tablets of three combination drugs containing 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) and benserazide hydrochloride (BNS) as APIs for treating Parkinson's disease were bisected; the resultant 10 samples were subjected to the JP content uniformity tests. We found that acceptance values of L-DOPA and BNS were 11.0-21.9% and 13.3-17.5%, respectively, with some non-conformity to the maximum allowed acceptance value (15.0%) as per the current JP. Image analyses by near IR showed that L-DOPA, BNS, lactose, and corn starch were uniformly distributed in each tablet; moreover, LF Raman spectroscopy imaging also supported the result that L-DOPA, BNS, and lactose were evenly distributed. Therefore, drug content in the tablets was uniform; thus, careful manipulation was recommended in the tablet bisection. However, the results of bisection line specifications and hardness tests revealed that the ease of division differed depending on the tablets, which warrants attention.

Wearable Electrochemical Microneedle Sensor for Continuous Monitoring of Levodopa: Toward Parkinson Management.

Levodopa is the most effective medication for treating Parkinson's disease (PD). However, because dose optimization is currently based on patients' report of symptoms, which are difficult for patients to describe, the management of PD is challenging. We report on a microneedle sensing platform for continuous minimally invasive orthogonal electrochemical monitoring of levodopa (L-Dopa). The new multimodal microneedle sensing platform relies on parallel simultaneous independent enzymatic-amperometric and nonenzymatic voltammetric detection of L-Dopa using different microneedles on the same sensor array patch. Such real-time orthogonal L-Dopa sensing offers a built-in redundancy and enhances the information content of the microneedle sensor arrays. This is accomplished by rapid detection of L-Dopa using square-wave voltammetry and chronoamperometry at unmodified and tyrosinase-modified carbon-paste microneedle electrodes, respectively. The new wearable microneedle sensor device displays an attractive analytical performance with the enzymatic and nonenzymatic L-Dopa microneedle sensors offering different dimensions of information while displaying high sensitivity (with a low detection limit), high selectivity in the presence of potential interferences, and good stability in artificial interstitial fluid (ISF). The attractive analytical performance and potential wearable applications of the microneedle sensor array have been demonstrated in a skin-mimicking phantom gel as well as upon penetration through mice skin. The design and attractive analytical performance of the new orthogonal wearable microneedle sensor array hold considerable promise for reliable, continuous, minimally invasive monitoring of L-Dopa in the ISF toward optimizing the dosing regimen of the drug and effective management of Parkinson disease.

Entacapone detection by a GOQDs-molecularly imprinted silica fluorescent chemical nanosensor.

A sensitive fluorescent chemical nanosensor for the detection of entacapone (EN) in pharmaceutical samples is introduced. EN is a nitrocatechol drug that functions as a selective and reversible inhibitor of catechol-O-methyl transferase and is widely prescribed in the treatment of Parkinson disease. Molecularly imprinting technology and graphene oxide quantum dots (GOQDs) were employed in designing the EN fluorescent nanosensor. GOQDs were embedded into an inorganic polymer while the imprinting process occurred. The synthesized GOQDs-embedded silica molecularly imprinting polymer (SMIP) showed strong fluorescent emission at 450 nm by exciting at 360 nm. The fluorescence intensity of GOQDs-embedded SMIP was quenched effectively by adsorption of EN as a template molecule. The quenching corresponded to EN concentration in a linear range of at least 0.40-6.00 µM with a limit of detection of 0.31 µM. The designed chemical nanosensor was successfully applied to the analysis of entacapone in some pharmaceutical tablets also containing carbidopa and levodopa (RSD 3.8%).

A novel electrochemical nanosensor based on NH2-functionalized multi walled carbon nanotubes for the determination of catechol-orto-methyltransferase inhibitor entacapone.

In this study, an antiparkinson drug Entacapone (ENP) is electrochemically investigated under optimized conditions using NH2 functionalized multi walled carbon nanotubes (NH2fMWCNT) decorated over glassy carbon electrode (GCE). The surface morphology of the NH2fMWCNT/GCE was probed by scanning electron microscopy (SEM) armed with EDX analysis. Electrochemical impedance spectroscopy (EIS) was employed to investigate the electron transfer capability of modified and bare electrodes. Cyclic voltammetry was used to compare the redox response of ENP on the surface of modified and unmodified electrodes. The influence of interfering agents was also studied to examine the selectivity of the designed sensor. For the purpose of practical applicability of the proposed method, differential pulse voltammetric method was applied for the investigation of ENP in real samples i.e., tablet, human serum and urine. Almost 100% recovery percentages were obtained from tablet, serum and urine samples with RSD% values of less than 2% for all the samples, thus, suggesting promising applicability of the designed electrochemical sensing platform (NH2fMWCNT/GCE) for determination of ENP in pharmaceutical dosage and real samples.

Simultaneous determination of FLZ and its metabolite (M1) in human plasma and urine by UHPLC-MS/MS: Application to a pharmacokinetic study.

FLZ is a novel anti-Parkinson's disease candidate drug. The main active metabolite is FLZ O-dealkylation (M1) in preclinical studies. A reliable ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) quantitation method was developed for the simultaneous determination of FLZ and M1 with low limits of quantitation in human plasma (0.1 ng/mL) and urine (0.5 ng/mL). The plasma and urine samples were both purified by full-automatic solid phase extraction (SPE) method with ensured high extraction recovery and little matrix effect for both analytes, and then separated on a BEH C18 column (2.1 × 50 mm, 1.7 µm). Detection and quantification were performed using an electrospray ionization (ESI) source in positive mode by multiple reaction monitoring (MRM). The precursor to product ion transitions were monitored at m/z 450.3+→313.2+ for FLZ, m/z 436.3+→299.1+ for M1, m/z 462.6+→142.0+ for [D12]-FLZ (internal standard of FLZ) and m/z 447.2+→125.2+ for [D11]-M1 (internal standard of M1), respectively. This method showed good linearity, accuracy, precision and stability in the range of 0.1-100 ng/mL in plasma and 0.5-500 ng/mL in urine of two analytes. Finally, the developed method was successfully applied to a pharmacokinetic research in Chinese healthy volunteers after oral administration of FLZ tablets.

Improved Bioavailability of Levodopa Using Floatable Spray-Coated Microcapsules for the Management of Parkinson's Disease.

Oral administration of levodopa (LD) is the gold standard in managing Parkinson's disease (PD). Although LD is the most effective drug in treating PD, chronic administration of LD induces levodopa-induced dyskinesia. A continuous and sustained provision of LD to the brain could, therefore, reduce peak-dose dyskinesia. In commercial oral formulations, LD is co-administrated with an AADC inhibitor (carbidopa) and a COMT inhibitor (entacapone) to enhance its bioavailability. Nevertheless, patients are known to take up to five tablets a day because of poor sustained-releasing capabilities that lead to fluctuations in plasma concentrations. To achieve a prolonged release of LD with the aim of improving its bioavailability, floatable spray-coated microcapsules containing all three PD drugs were developed. This gastro-retentive delivery system showed sustained release of all PD drugs, at similar release kinetics. Pharmacokinetics study was conducted and this newly developed formulation showed a more plateaued delivery of LD that is void of the plasma concentration fluctuations observed for the control (commercial formulation). At the same time, measurements of LD and dopamine of mice administered with this formulation showed enhanced bioavailability of LD. This study highlights a floatable, sustained-releasing delivery system in achieving improved pharmacokinetics data compared to a commercial formulation.

Development and Validation of a Robust and Efficient HPLC Method for the Simultaneous Quantification of Levodopa, Carbidopa, Benserazide and Entacapone in Complex Matrices.

PURPOSE: A variety of fixed-dose combination products is used in the therapy of Parkinson Disease. However, to date a proper analytical method applicable for comparative screening of different antiparkinson products was not available. The objective of the present work was thus to develop and validate an analytical method for the simultaneous quantification of levodopa, carbidopa, benserazide and entacapone. The method should be applicable for quantifying samples from drug release experiments with marketed products and prototype formulations performed under compendial and biorelevant test conditions. METHODS: A fast and robust method applicable for separation and quantification of the four compounds was developed and validated according to International Conference on Harmonization guidelines. Method validation covered applicability to a wide concentration range of all compounds and peak separation in complex sample matrices such as biorelevant dissolution media. RESULTS: The compounds were successfully separated by using a gradient elution method on an endcapped LiChrospher 100 RP-18 (250 x 4.6 mm, 5 µm) column coupled with a LiChrospher 100 RP-18 precolumn (4 x 4 mm, 5 µm) at a column temperature of 35.0 °C and a flow rate of 1.50 mL/min. The injection volume was 30 µL and the detection wavelengths were 280 and 210 nm, respectively. For all drug/media combinations the method was linear (r2 > 0.999) for a concentration range corresponding to 1.25 - 125 % label claim (i.e. 200 mg levodopa/entacapone and 50 mg carbidopa/benserazide) released. All other validation parameters were in the specified limits over the same concentration range. CONCLUSION: The new method allows for robust and fast separation of levodopa, carbidopa, benserazide and entacapone without any interference caused by excipients or ingredients of compendial and biorelevant dissolution media and thus presents a valuable tool in both formulation development and in vitro drug release screening of numerous fixed-dose combinations of antiparkinson drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Optimization of o-phtaldialdehyde/2-mercaptoethanol postcolumn reaction for the hydrophilic interaction liquid chromatography determination of memantine utilizing a silica hydride stationary phase.

A rapid procedure for the determination of memantine based on hydrophilic interaction chromatography with fluorescence detection was developed. Fluorescence detection after postcolumn derivatization with o-phtaldialdehyde/2-mercaptoethanol was performed at excitation and emission wavelengths of 345 and 450 nm, respectively. The postcolumn reaction conditions such as reaction temperature, derivatization reagent flow rate, and reagents concentration were studied due to steric hindrance of amino group of memantine. The derivatization reaction was applied for the hydrophilic interaction liquid chromatography method which was based on Cogent Silica-C stationary phase with a mobile phase consisting of a mixture of 10 mmol/L citric acid and 10 mmol/L o-phosphoric acid (pH 6.0) with acetonitrile using an isocratic composition of 2:8 v/v. The benefit of the reported approach consists in a simple sample pretreatment and a quick and sensitive hydrophilic interaction chromatography method. The developed method was validated in terms of linearity, accuracy, precision, and selectivity according to the International Conference on Harmonisation guidelines. The developed method was successfully applied for the analysis of commercial memantine tablets.

A novel way for detection of antiparkinsonism drug entacapone via electrodeposition of silver nanoparticles/functionalized multi-walled carbon nanotubes as an amperometric sensor.

Silver (Ag) nanoparticles were electrochemically deposited on the film of a metformin functionalized multi-walled carbon nanotube modified glassy carbon electrode (Met-MWCNT/GCE), which fabricated an Ag@Met-MWCNT nanocomposite sensor (Ag@Met-MWCNT/GCE) to detect entacapone (ENT). The Ag@Met-MWCNT nanocomposite was characterized by field emission scanning electrochemical microscopy (FESEM), X-ray diffraction (XRD) analysis, FT-IR and electrochemical tests. The modified electrode showed a large electrocatalytic activity for reduction of ENT. This improved activity indicates that Met@MWCNT plays a crucial role in the dispersion and stabilization of Ag nanoparticles on GCE. Under the optimized conditions the linear range for the detection of the ENT was obtained to be 0.05 to 70.0µM with a low detection limit of 15.3nM. The proposed sensor can effectively analyse ENT concentration in pharmaceutical formulations and human urine samples, avoiding interference, and is a promising ENT sensor due to good sensitivity, stability and low cost.

Quantitation of memantine hydrochloride bulk drug and its tablet formulation using proton nuclear magnetic resonance spectrometry.

The use of quantitative nuclear magnetic resonance spectrometry for the determination of non-UV active memantine hydrochloride with relative simplicity and precision has been demonstrated in this study. The method was developed on a 500 MHz NMR instrument and was applied to determination of the drug in a tablet formulation. The analysis was performed by taking caffeine as an internal standard and D2 O as the NMR solvent. The signal of methyl protons of memantine hydrochloride appeared at 0.75 ppm (singlet) relative to the signal of caffeine (internal standard) at 3.13 ppm (singlet). The method was found to be linear (r(2) = 0.9989) in the drug concentration range of 0.025 to 0.80 mg/ml. The maximum relative standard deviation for accuracy and precision was <2. The limits of detection and quantification were 0.04 and 0.11 mg/ml, respectively. The robustness of the method was revealed by changing nine different parameters. The deviation for each parameter was also within the acceptable limits. The study highlighted possibility of direct determination of memantine hydrochloride in pure form and in its marketed tablet formulation by the use of quantitative NMR, without the need of derivatization, as is the requirement in HPLC studies. Copyright © 2016 John Wiley & Sons, Ltd.

Validation of high performance liquid chromatographic and spectrophotometric methods for the determination of the antiparkinson agent pramipexole dihydrochloride monohydrate in pharmaceutical products

abstract The antiparkinson agent pramipexole dihydrochloride monohydrate was quantified in pharmaceutical products by high performance liquid chromatography (HPLC) and derivative spectrophotometry. The first method was based on HPLC using tamsulosin HCl as an internal standard. In this method, chromatographic separation was achieved using a LiChrospher 60 RP column at 25°C, with a flow rate of 1.0 mL/min at 263 nm. The eluent comprised 0.01 mol/L ammonium acetate (pH 4.4) and acetonitrile (35:65 by volume). The linearity range was found to be 10.0-30.0 µg/mL with a mean recovery of 100.5 ± 1.10. The limit of detection (8 ng/mL) and limit of quantification (50 ng/mL) were calculated. In the second method, the first derivative spectrophotometric technique for the determination of pramipexole dihydrochloride monohydrate was performed by measuring the amplitude at 249 and 280 nm. In the first derivative technique, the absorbance and concentration plot was rectilinear over the 5.0-35.0 µg/mL range with a lower detection limit of 1.5 ng/mL and quantification limit of 4.5 ng/mL. The typical excipients included in the pharmaceutical product do not interfere with the selectivity of either method. The developed methods were validated for robustness, selectivity, specificity, linearity, precision, and accuracy as per the ICH and FDA guidelines (ICH Q2B, 1996; FDA,2000). In conclusion, the developed methods were successful in determining the quantity of the antiparkinson agent pramipexole dihydrochloride monohydrate in pharmaceutical products. The RSD values for the pharmaceutical product used in this study were found to be 0.97% for the HPLC method and 0.00% for the first derivative spectrophotometric method.

resumo O fármaco antiparkinsoniano, dicloridrato de pramipexol monoidratado, foi quantificado no produto farmacêutico por cromatografia líquida de alta eficiência (CLAE) e espectrofotometria derivada. No primeiro método baseado na CLAE, o cloridrato de tansulosina foi usado como padrão interno. Nesse método, a separação cromatográfica foi realizada usando uma coluna Lichrosper 60 RP a 25 °C e acetato de amônio 0,01 mol/L (pH:4.4): acetonitrila (35:65 em volume) como eluente com fluxo de 1,0 mL /min a 263 nm. A faixa de linearidade foi de 10.0-30.0 µg/mL com média da recuperação 100.5 ± 1.10. O limite de detecção (8 ng/mL) e o limite de quantificação (50 ng/mL) foram calculados. Por outro lado, a primeira técnica de espectrofotometria derivada para a determinação de dicloridrato de pramipexol monoidratado foi realizada através da medida da amplitude a 249 e 280 nm. Na técnia da primeira derivada, a absorvância e a plotagem da concentração foi retilínea na faixa de 5.0-35.0 µg/mL com limite inferior de detecção de 1.5 ng/mL e limite de quantificação de 4.5 ng/mL. Os excipientes típicos incluídos no produto farmacêutico não interferem com a seletividade dos métodos. Os métodos desenvolvidos foram validados quanto à robustez, seletividade, especificidade, linearidade, precisão e exatidão de acordo com as diretrizes do ICH e FDA (ICH Q2B,1996; FDA,2000). Concluindo, os métodos propostos foram aplicados com sucesso para a determinação quantitativa do agente antiparkinsoniano dicloridrato de pramipexol monoidrato em produtos farmacêuticos. Os valores de RSD para o produto farmacêutico utilizado neste estudo foi 0.97% para a CLAE e 0.00% para o método de espectrofotometria de primeira derivada.

HPLC-UV method development and validation for the quantification of ropinirole in new PLGA multiparticulate systems: Microspheres and nanoparticles.

A simple HPLC-UV method was developed and validated for the quantitation of RP free base encapsulated into two new multiparticulate systems (microparticles and nanoparticles), as well as for the quantification of RP hydrochloride when given as a loading dose together with the new delivery system developed. HPLC separation was achieved using a C18 Kromasil column (250 mm × 4 mm) with a mobile phase composed of acetonitrile-phosphate buffer solution (55:45, v/v) adjusted at pH 6.0 and containing 0.3% triethanolamine. Flow rate was set at 1.0 mL min(-1). The UV detector was operated at 245 nm. The method allowed for the simultaneous determination of both RP and RP-HCl. The method was linear within the range 2.5-50 µg mL(-1) for both RP and RP-HCl. The limits of detection (LOD) and quantitation (LOQ) found were 0.8 µg mL(-1) and 2.4 µg mL(-1) for RP, and 0.3 µg mL(-1) and 0.9 µg mL(-1) for RP-HCl. The method was found to be simple, rapid, specific, precise, accurate, and reproducible. The method was successfully applied to the determination of the encapsulation efficiency of RP in the multiparticulate systems developed, being 85.03 ± 3.77% and 51.12 ± 3.50%, for RP-loaded PLGA microspheres and RP-loaded PLGA nanoparticles, respectively.

Comparison of the antioxidant potential of antiparkinsonian drugs in different in vitro models

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Furthermore, oxidative stress plays a role in PD, causing or contributing to the neurodegenerative process. Currently PD has only symptomatic treatment and still nothing can be done to stop the degenerative process of the disease. This study aimed to comparatively evaluate the antioxidant capacity of pramipexole, selegeline and amantadine in different in vitro studies and to offer possible explanations on the molecular antioxidant mechanisms of these drugs. In vitro, the antioxidant capacity of the drugs was assessed by the ability of antiparkinsonian drugs to decrease or scavenge ROS in the neutrophil respiratory burst, ability of antiparkinsonian drugs to donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), to scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid (ABTS+) and evaluation of the ferric reducing antioxidant power (FRAP). This study demonstrated that both pramipexole and selegiline, but not amantadine, have antioxidant effects in vitro by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS+ assay and presenting ferric reduction antioxidant power. This chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs beyond their already recognized mechanism of action.

A doença de Parkinson (DP) é caracterizada pela degeneração progressiva dos neurônios dopaminérgicos na substância negra pars compacta. Além disso, o estresse oxidativo, presente nesta doença, causa ou contribui para o processo neurodegenerativo. Atualmente, a DP tem apenas tratamento sintomático e ainda nada pode ser feito para interromper o processo degenerativo. Este estudo teve como objetivo avaliar, comparativamente, a capacidade antioxidante do pramipexol, selegilina e amantadina em diferentes testes in vitro e oferecer possíveis explicações sobre os mecanismos moleculares antioxidantes destes fármacos. Avaliou-se a atividade antioxidante dos fármacos através da capacidade em diminuir ou sequestrar espécies reativas de oxigênio no burst respiratório, da capacidade em doar hidrogênio e estabilizar o radical livre 2,2-difenil-1-picril-hidrazil (DPPH•), de remover o radical 2,2'-azino-di-(3-etilbenzotiazolina-6-sulfônico (ABTS+) e da verificação do poder redutor/antioxidante do ferro (FRAP). Este estudo demonstrou que tanto o pramipexol como a selegilina, mas não a amantadina, possuem efeitos antioxidantes in vitro por eliminar o ânion superóxido no burst respiratório, doar elétrons no método ABTS e apresentar poder redutor sobre o ferro (FRAP). Essa capacidade antioxidante pode estar relacionada com a estrutura química desses medicamentos, sugerindo possíveis mecanismos neuroprotetores destes fármacos além de seus mecanismos de ação já conhecidos.

A biomimetic potentiometric sensor based on molecularly imprinted polymer for the determination of memantine in tablets.

Memantine hydrochloride is one of the first novel class medications for treatment of Alzheimer's disease. In this work, a biomimetic potentiometric sensor, based on a non-covalent imprinted polymer, was fabricated for the recognition and determination of memantine in pure drug and tablet pharmaceutical form. The molecularly imprinted polymer was synthesized by precipitation polymerization, using memantine hydrochloride as a template molecule, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linking agent. The sensor was developed by dispersing the memantine imprinted polymer particles in dibutyl sebacate plasticizer and embedding in poly(vinyl chloride) matrix. The wide linear range (10(-5) -10(-1) M), with a near Nernstian response of 57.4 mV/decade, a limit of detection 6.0 × 10(-6) M, fast response time (~15 s) and a satisfactory long-term stability (4 months) are characterizations of the proposed sensor. The sensor showed a high selectivity and a sensitive response to the template in aqueous system. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode. It was used as indicator electrode in potentiometric determination of memantine in pharmaceutical formulations.

A fatal intoxication case involving ropinirole.

Ropinirole, a specific non-ergoline dopamine D2-receptor agonist, belongs to the drugs applied in treatment of Parkinson's disease (PD) and restless legs syndrome (RLS) and acts as a D2, D3, and D4 dopamine receptor agonist with highest affinity for D3. Therapeutic ropinirole plasma levels in adults are defined between 0.4 and 6 ng/mL. This case report documents a fatal intoxication involving ropinirole. Information about lethal ropinirole concentrations is hitherto lacking in the literature and the assessed ropinirole levels of this case may present a step towards defining potentially lethal concentrations. A 37-year-old man without medical history was found dead in a converted van used as place of residence and an autopsy was performed. The pathological findings did not reveal an apparent cause of death but the toxicological analysis revealed the presence of ropinirole, paracetamol, and alcohol in the peripheral blood sample. Quantitative analysis revealed that ropinirole was present at a peripheral blood concentration of 64 ng/mL. The ropinirole concentrations determined in vitreous humor, urine and bile were respectively, 11 ng/mL, 2670 ng/mL and 826 ng/mL. Paracetamol was detected at a blood level of <2 µg/mL. Based on the autopsy findings and toxicological results, the cause of death was primarily attributed to intoxication with ropinirole in combination with alcohol.

Electrocatalytic oxidation and voltammetric determination of levodopa in the presence of carbidopa at the surface of a nanostructure based electrochemical sensor.

In the present paper, the use of a carbon paste electrode modified by meso-tetrakis(3-methylphenyl) cobalt porphyrin (CP) and TiO(2) nanoparticles for the determination of levodopa (LD) and carbidopa (CD) was described. Initially, cyclic voltammetry was used to investigate the redox properties of this modified electrode at various scan rates. Next, the mediated oxidation of LD at the modified electrode was described. At the optimum pH of 7.0, the oxidation of LD occurs at a potential about 150 mV less positive than that of an unmodified carbon paste electrode. Based on differential pulse voltammetry (DPV), the oxidation of LD exhibited a dynamic range between 0.1 and 100.0 µM and a detection limit (3σ) of 69 ± 2 nM. DPV was used for simultaneous determination of LD and CD at the modified electrode, and quantitation of LD and CD in some real samples (such as tablets of Parkin-C Fort and Madopar, water, urine, and human blood serum) by the standard addition method.

Citrate-capped Mn-modified CdSe/CdS quantum dots as luminescent probes for levodopa detection in aqueous solution.

A novel kind of citrate capped Mn-modified CdSe/CdS quantum dots (QDs) was developed. The Mn-modified CdSe/CdS QDs had a narrow, symmetric emission and strong fluorescence with quantum yield over 41%. The interaction between the QDs and levodopa was investigated. The results showed that levodopa selectively quenched the fluorescence intensity of the QDs. Based on the fluorescence quenching of the synthesized QDs by levodopa, a simple, rapid and specific quantitative method for levodopa was proposed. The factors affecting the fluorescence detection for levodopa were studied. Under the optimum conditions, the quenched intensity of the fluorescence versus levodopa concentration from 1 to 100 µM gave a linear response with an excellent correlation coefficient of 0.9996, and the limit of detection (3σ/K) was 2 × 10(-7)M. The contents of levodopa in pharmaceutical tablets were determined by the proposed method and the results agreed with the claimed values.