Co-formulated Drugs Research Articles

Monitoring of Clotrimazole Degradation Pathway in Presence of its Co-formulated Drug.

Two stability-indicating chromatographic methods for the determination of clotrimazole and its two acid induced degradation products, with dexamethasone acetate without prior separation. First method depends on RP-HPLC utilizing ODS-3 Inertsil C18 column. Mobile phase consists of acetonitrile:phosphate buffer (pH 6.0) in ratio (65:35, v/v) with flow rate 1.5 mL/min and UV-detection at 220 nm. Linearity range 1.0-75.0 μg/mL for clotrimazole and 2.0-75.0 μg/mL for dexamethasone with mean percentage recovery of 99.49 ± 1.10 for CLT and 99.60 ± 1.06 for DA. Second method depends on HP-TLC. Developing system is composed of chloroform:ethyl acetate in the ratio of (5:3.5, v/v), scanned at 220 nm. Linearity range 1.0-12.0 μg/band for clotrimazole and 1.0-20.0 μg/band for dexamethasone with mean R% of 99.33 ± 0.76 for clotrimazole and 99.77 ± 0.99 for dexamethasone. Conditions and parameters affecting the separation of the cited components without interference of the degradation products are tested and optimized. Suitability of the methods for quantization of the drugs concentrations is proven by validation as instructed from the ICH. Validation results and statistical treatment of the data demonstrate reliability of these methods. Kinetics of acid degradation process of clotrimazole are investigated by the proposed HPLC method and the order rate constant, half life and shelf life are computed.

Spectrophotometric Resolution and Quantification of Ternary Co-formulated Mixture of Thioctic acid, Benfotiamine and Cyanocobalamin

Four spectrophotometric methods were developed and validated for spectral resolution and determination of thioctic acid (THC), benfotiamine (BEN) and cyanocobalamin (CNCo) in their pure form, laboratory prepared mixtures and capsules. Method A, a first derivative method for determination of CNCo, by recording the peak amplitude at 564.0 nm. Method B, is a Ratio difference spectrophotometric one which is applied for determination of THC and BEN, where CNCo has no interference. Method C applied first derivative of ratio spectra where THC and BEN were determined by recording the peak amplitude at 330.8 and 286.8 nm, in order. Method D a Ratio subtraction method that was successfully determines BEN at its ?max without interference of the other co-formulated drugs. Validation according to ICH guidelines was performed. The linearity ranges were 200.00-1800.00, 2.00-30.00 and 10.00-200.00 µg/mL for THC, BEN and CNCo, in a respective order. The methods were found to be accurate, precise and specific.

Novel spectrofluorimetric approach for determination of ledipasvir through UV-irradiation: application to biological fluids, pharmacokinetic study and content uniformity test.

A highly sensitive and specific fluorescence dependent approach was created for quantitation of a recently approved anti-HCV drug (ledipasvir). This approach relies on the innovative enhancement in fluorescence intensity of ledipasvir upon exposing the cited drug to direct UV irradiation as a photo-physical fluorescence enhancer. The fluorescence of the resultant solution was measured at an emission peak of 375 nm (321 nm excitation). The photoluminescence properties of the resultant product were carefully examined and the quantitative rectilinear concentration plot for the method was 5.0–150.0 ng mL−1 with a detection limit of 0.9 ng mL−1 and a quantitation limit of 2.7 ng mL−1. The excellent analytical features of the proposed method allow to the specific and sensitive estimation of ledipasvir either in plasma samples or in tablet dosage form without any interference from pharmaceutical excipients or other co-formulated anti-HCV drugs (sofosbuvir). The developed analytical and bio-analytical procedures were created and validated according to ICH guidelines and FDA guidelines, respectively. Since the main elimination route for ledipasvir is via faecal excretion, the studied drug was determined for the first time in faecal samples by the method with adequate recovery. Moreover, the pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0–t, and AUC0–∞) for ledipasvir were determined by the proposed method. Additionally, the proposed method was successfully applied for supervising the content uniformity for ledipasvir in its pharmaceutical tablets.

Validated potentiometric method for the determination of sulfacetamide sodium; application to its pharmaceutical formulations and spiked rabbit aqueous humor

Specific, accurate and precise electrochemical method was developed and validated for the determination of sulfacetamide sodium in presence of its co-formulated drug (prednisolone acetate) and its pharmacopoeial impurities. The method was based on fabrication of membrane sensor. The characteristics of electrochemical response were estimated, and the proposed sensor displayed excellent characteristics for the determination of sulfacetamide sodium in bulk powder, laboratory prepared mixtures, dosage forms and in spiked biological fluid (Rabbit aqueous humor). The sensor was constructed through the use of tetradodecylammonium bromide (TDB) as an anion exchanger and 2-nitrophenyl octyl ether (NPOE) as a plasticizer in polyvinyl chloride (PVC) matrix. The performance characteristics, sensitivity and selectivity were evaluated according to IUPAC guidelines. Linearity was achieved over the concentration range of 1 × 10−4.5–1 × 10−2 M with Nernstian slope of 51.086 mV/decade over the pH range of 5–7. The sensor showed a rapid response (10–15 s) and good stability (up to 4 weeks). The obtained results were statistically compared with the official methods and no significant difference was found regarding accuracy and precision.

Resolution and Quantitation of Triamcinolone Acetonide and Its Coformulated Drug in the Presence of Its Impurities and Degradation Products by HPTLC and HPLC.

Two specific, sensitive, and precise stability-indicating chromatographic methods have been developed for the determination of triamcinolone acetonide (TMC) and its coformulated drug, econazole nitrate (ECZ), in the presence of TMC impurities and degradation products. The first method was based on HPTLC-spectrodensitometry in which resolution and quantitation was achieved by using silica gel 60 F254 HPTLC plates and an ethyl acetate-tetrahydrofuran-ammonia mobile phase (10.0 + 7.0 + 0.1, v/v/v). The second method was a reversed-phase HPLC method in which separation was achieved using an acetonitrile-methanol-0.05 M potassium dihydrogen phosphate mobile phase, pH 3.0 (25.0 + 15.0 + 60.0, v/v/v). In both methods, the separated components were detected at 225 nm. Validation of both methods was conducted in compliance with International Conference on Harmonization (ICH) guidelines, and system suitability was confirmed. The linearity ranges were 0.20-28.00 and 0.50-55.00 µg/band for TMC and ECZ by HPTLC, whereas for HPLC, the range was 0.05-30.00 and 1.00-40.00 µg/mL for both drugs, respectively. The methods were successfully applied for the analysis of a pharmaceutical formulation and were compared with the reported method with no significant difference.

Different resolution techniques for management of overlapped spectra: Application for the determination of novel co-formulated hypoglycemic drugs in their combined pharmaceutical dosage form

To maintain intensive glucose control early in the type II diabetes mellitus process, novel combinations of canagliflozin/metformin (CAG/MEF) and empagliflozin/linagliptin (EMG/LIG) offer particular treatment benefits. In this study, sensitive and precise spectrophotometric methods were developed for the determination of such hypoglycemic drug combinations in bulk powder and in pharmaceutical dosage form without prior separation. The first method was ratio difference coupled with modified isosbestic point technique where the amplitude difference between 239 and 291 nm on the ratio spectrum of CAG obtained using 4 μg/ml of MEF as divisor was used for determination of CAG. On the other hand, MEF was estimated using a modified isosbestic spectrophotometric method, where the total concentration of CAG and MEF in mixture could be calculated at 250 nm (isosbestic point) after multiplication by a correction factor. Then concentration of MEF could be calculated by subtraction. The second method was ratio subtraction coupled with extended ratio subtraction, where EMG was determined at 225 nm by subtraction of plateau values from the ratio spectrum followed by multiplication with the spectrum of 6.5 μg/ml of LIG (divisor). Then, an extension of the normal ratio subtraction method was performed in order to determine LIG at 226 nm. Linearity was obtained over 5–30, 2.5–16, 2.5–16 and 1.25–8 μg/ml for CAG, MEF, EMG and LIG, respectively. The developed methods were successfully applied for the determination of studied drugs in tablets. Validation parameters were found to be within acceptance limits, thus confirming methods accuracy and selectivity. The obtained results were statistically compared with the reported one showing no significant difference in terms of accuracy and precision. The methods could be applied for routine analysis of the cited drugs in quality control laboratories.

Advanced chemometrics manipulation of UV-spectroscopic data for determination of three co-formulated drugs along with their impurities in different formulations using variable selection and regression model updating

Multivariate calibration models manipulating UV-spectroscopic data of three anti-productive cough drugs namely ambroxol, guaifenesin and theophylline were constructed for the intent of simultaneous determination in presence of their impurities; guaiacol and caffeine. Both interval partial least squares (iPLS) and synergy interval partial least square (siPLS) algorithms were adopted for variables selection to extract useful information and improve the models' performance. The optimal spectral range and their combinations were assigned according to the lowest value of Root Mean Square Error of Prediction (RMSEP), Standard Error of Prediction (SEP) and Correlation Coefficient (R2). The results obtained from full spectrum PLS were compared with those obtained by iPLS and siPLS. The siPLS method exhibited better performance. The combination of four subintervals, 2, 9, 13, and 16, showed the best effect, with RMSEP of 0.1039, 0.3548 and 0.207 μg/mL, for ambroxol, guaifenesin and theophylline, respectively and correlation coefficient of 0.9999, 0.9975 and 0.9994 for ambroxol, guaifenesin and theophylline, respectively. The proposed methods were used for the simultaneous determination of the three drugs in presence of their impurities in bulk powder and in pharmaceutical formulation.

Challenges for the pharmaceutical technical development of protein coformulations.

This review discusses challenges to stability, analytics and manufacturing of protein coformulations. Furthermore, general considerations to be taken into account for the pharmaceutical development of coformulated protein drug products are highlighted. Coformulation of two or more active substances in one single dosage form has recently seen increasing use offering several advantages, such as increased efficacy and/or the overall reduction of adverse event incidents in patients. Most marketed coformulated drug products are composed of small molecules. As proteins are not only comparatively large but also complex molecules, the maintenance of their physicochemical integrity within a formulation throughout pharmaceutical processing, storage, transport, handling and patient administration to ensure proper pharmacokinetics and pharmacodynamics in vivo already represents various challenges for single-entity products. Thus, nowadays, only sparse biologics-based coformulations can be found, as additional complexity during development is given for these products. The complexity of the dosage form and the protein molecules results into additional challenges to formulation, manufacture, storage, transport, handling and patient administration, stability and analytics during the pharmaceutical development of protein coformulations. Various points have to be considered during different stages of development in order to obtain a safe and efficacious product.

Smart bi-metallic perovskite nanofibers as selective and reusable sensors of nano-level concentrations of non-steroidal anti-inflammatory drugs

A strategy for trace-level carbon-based electrochemical sensors is investigated via exploring the interesting properties of BaNb2O6 nanofibers (NFs). Utilizing adsorptive stripping square wave voltammetry (ASSWV), an electrochemical sensing platform was developed based on BaNb2O6 nanofibers-modified carbon paste electrode (CPE) for the sensitive detection of lornoxicam (LOR). Different techniques were used to characterize the fabricated BaNb2O6 perovskite NFs. The obtained data show the feasibility to electro-oxidize LOR and paracetamol (PAR) on the surface of the fabricated sensor. The amount of nanofiber and testing conditions were optimized using response surface methodology and ASSWV technique. The optimized BaNb2O6/CPE sensor exhibits low detection limit of 6.39 × 10−10 mol L−1, even in the presence of the co-formulated drug paracetamol (PAR). The sensor was successfully applied for biological applications.

A Green Method for the Determination of Mebeverine in Its Pharmaceutical Products and Human Serum Based On Diatom Modified Carbon Paste Electrode Using Square Wave Adsorptive Anodic Stripping Voltammetry (SW-AdASV)

AbstractThe first use of a green method of analysis using diatom for trace determination of mebeverine in its pharmaceutical formulation and human serum based on its great properties such as high surface area, hydrophilicity, and adsorption. in addition to diatom requires no chemical modification. Characterization of Diatom using FTIR showed bands corresponding to AlMgOH, Si-O-Al, SiOH, and OH, while XRD showed that diatom is amorphous containing silica of quartz crystal shape, SEM revealed that diatom has porous surface. Cyclic Voltammetry of the modified electrode revealed that the modified electrode has higher surface area and greater adsorption. Mebeverine hydrochloride (MV.HCl) was determined based on 5% diatom modified carbon paste electrode 5% (w/w)DA/CPE as a sensor with LOD and LOQ of 1.80×10−9 and 6.00×10−9 respectively. Then, the modified electrode was successfully applied for the trace determination of MV.HCl in different pharmaceutical preparations; “Coloverin A”, “Colona” and “Colofac” tablets without interferences from excipients and co-formulated drugs. The achieved detection limit in human serum was 8.0×10−9 M. The described adsorptive anodic stripping voltammetric method is reliable, simple, and sensitive enough for assay of MV.HCl in real plasma samples, pharmacokinetic studies, quality control and assurance of the drug in industry and in clinical laboratories.

Ultrasensitive spectrofluorimetric method for rapid determination of daclatasvir and ledipasvir in human plasma and pharmaceutical formulations

Direct-acting antivirals (DAAs) represent a revolution in the treatment of chronic hepatitis C which have emerged at an extremely rapid pace over the past few years. DAAs act directly on the hepatitis C virus at various points in the viral life cycle to inhibit viral production. Among these novel DAAs, are daclatasvir (DCS) and ledipasvir (LDS). Herein, a novel, fast, simple, ultrasensitive and cost-effective spectrofluorimetric method was designed for determination of DCS and LDS in miscellaneous matrices. The method is based on investigation of the native fluorescence of the cited drugs. The relative fluorescence intensity (RFI) was measured at λex/λem equal to 315/381 nm for DCS and 332/387 nm for LDS. Under the optimum conditions, the linear ranges of calibration curves were 0.2–30 and 6–120 ng mL−1 for DCS and LDS, respectively with correlation coefficients ≥0.9998. The detection limits were 0.047 and 1.939 ng mL−1 for DCS and LDS, respectively indicating ultrasensitivity of the proposed method. Consequently, this permits in vitro and in vivo application of the proposed method in spiked and real human plasma with good percentage recovery (96.6–103.6%). The method was validated in compliance with ICH guidelines and US-FDA guidelines. Furthermore, the application was extended to analysis of DCS and LDS in its pharmaceutical formulations (either alone or in presence of other co-formulated drugs) and in synthetic mixture with sofosbuvir or ribavirin.

Fast simultaneous quantitation of valsartan and amlodipine besylate using an eco-friendly micellar HPLC-UV method: application to spiked human plasma and content uniformity testing for amlodipine

A simple, sensitive, and economic quantitation of two co-formulated antihypertensive drugs, valsartan and amlodipine besylate was carried out in less than 4 minutes.

Simultaneous determination of codeine and its co-formulated drugs acetaminophen and caffeine by utilising cerium oxide nanoparticles modified screen-printed electrodes

We report a facile and low-cost methodology for the simultaneous determination of codeine (COD) and its common co-formulated drugs acetaminophen (APAP) and caffeine (CAF) utilising cerium oxide nanoparticles modified screen-printed electrodes (CeO2-SPEs) for the first time. Interestingly, CeO2-SPEs offer a promising, sensitive, robust and chemically stable non-enzymatic electrochemical sensor for the simultaneous determination of APAP, COD and CAF without any interference / overlapping of voltammetric peaks/signals. The electro-analytical sensing of APAP, COD and CAF were explored using CeO2-SPEs over a wide concentration range with competitively low detection limits (3S/N) of 0.051, 0.043 and 2.4 μmol L−1 respectively. The CeO2-SPEs with nanoscale CeO2 architectures exhibit practical analytical utility for the accurate and simultaneous determination of APAP, COD and CAF in human serum samples with excellent recoveries. The results show exceptional electrochemical performance of CeO2-SPEs in term of simplicity, stability and sensing abilities that can effectively reduce processing costs for scalable production and routine analysis.

Development and Validation of Eco-Friendly Liquid Chromatographic and Spectrophotometric Methods for Simultaneous Determination of Coformulated Drugs: Phenylephrine Hydrochloride and Prednisolone Acetate.

Five simple, sensitive, and eco-friendly LC and UV spectrophotometric methods have been developed for the simultaneous determination of phenylephrine hydrochloride (PHE) and prednisolone acetate (PRD) in their combined dosage form. The first method was reversed-phase (RP) LC using methanol-water-heptane-1-sulfonic acid sodium salt (75 + 25 + 0.1, v/v/w) as a mobile phase. Separation was achieved using an XSelect HSS reversed-phase C18 analytical column (250 × 4.6 mm, 5µm). The flow rate was 1.0 mL/min and UV detection was done at 230 nm. Quantification was achieved over the concentration ranges of 5-50 µg/mL for PHE and 2-90 µg/mL for PRD. Four spectrophotometric methods were proposed, namely dual wavelength, first derivative of ratio spectra, ratio difference, and mean-centering of ratio spectra. Linearity was observed in the concentration ranges of 10-120 and 5-35 µg/mL for PHE and PRD, respectively, for the spectrophotometric methods. Green solvents were used in the proposed methods because they play a vital role in the analytical methods' influence on the environment. The suggested methods were validated regarding linearity, accuracy, and precision according to the International Conference on Harmonization guidelines, with satisfactory results. These methods could be used as harmless substitutes for routine analysis of the mentioned drugs, with no interference from excipients.

Validated Stability-Indicating Derivative Spectrophotometry and Synchronous Fluorescence Spectroscopy Methods for the Determination of Dapoxetine Hydrochloride in the Presence of its Degradation Product and Co-Formulated Drugs

The stability of dapoxetine hydrochloride (DP) was studied in the presence of its acidic degradation product namely, (+)-N, N-dimethyl-1-phenyl-3-propanolamine (Deg 1) and the co-formulated drugs Vardenafil (VR) and Tadalafil (TD) using derivative spectrophotometry and synchronous fluorescence spectroscopy methods. Method I, stability indicating derivative spectrophotometry 1D was developed for the determination of DP in the presence of its hydrolytic degradation product and the co-formulated drug VR. The amplitude of the first derivative spectra 1D at λmax of 240 nm and 227 nm was measured for DP and VR, respectively. Method IIA, stability indicating synchronous fluorescence spectroscopy (SFS) was described for the determination of DP in the presence of its hydrolytic degradation product and the co-formulated drug TD. In this method (SFS) was performed at Δλ of 70 nm in acetonitrile medium and the synchronous fluorescence intensities of TD were measured at 212 nm. Method IIB, The first derivative synchronous fluorescence spectra FDSFS were applied for measuring the amplitudes of FDSFS at 295 nm and 242 nm for analysis of DP and TD, respectively. The degradation products was obtained in acidic stress condition of 5 M hydrochloric acid, separated, and identified by IR and mass spectrometry to confirm its structure, and elucidate degradation pathway. The methods were applied for stability-indicating assay of DP (method I and II), VR (method I) and TD (method II) in bulk powders, laboratory prepared mixtures and co-formulated pharmaceutical preparations containing degradation product of DP. The results obtained were satisfactory compared with those obtained from the comparison methods and no significant differences were found. The two stability indicating methods were validated as per ICH guidelines.

Green Ion Selective Electrode Potentiometric Application for the Determination of Cinchocaine Hydrochloride in Presence of Its Degradation Products and Betamethasone Valerate: A Comparative Study of Liquid and Solid Inner Contact Ion-Selective Electrode Membranes

The sustainable and green chemistry principles enable scientists to protect and benefit the economy, people and the planet by finding creative and innovative ways to reduce waste, conserve energy, and discover replacements for hazardous substances. In this work, an environmentally friendly ion selective electrode (ISE) potentiometric method was developed for the determination of cinchocaine hydrochloride (CIN) in presence of its degradation products either in bulk powder or in its combined pharmaceutical formulation with betametahsone valerate. Two novel CIN-selective electrodes were fabricated and evaluated. The fabrication of electrodes was based on sodium tetrakis [3,5-bis (trifluoromethyl)phenyl]borate as a cationic exchanger in a PVC matrix with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer and using 2-hydroxy propyl-β-cyclodextrin (2-HP β-CD) as an ionophore. A comparative study was conducted using two designed CIN-selective electrodes; a conventional liquid inner contact, sensor 1, and a glassy carbon solid contact electrode, sensor 2. Sensor 1 has a linear dynamic range of 3.0 × 10−5 mol L−1 to 1.0 × 10−2 mol L−1, with a Nernstian slope of 54.89 mV/decade and a detection limit of 5.01 × 10−6 mol/L. Sensor 2 shows linearity over the concentration range of 1.0 × 10−5 mol L−1 to 1.0 × 10−2 mol L−1, with a Nernstian slope of 57.01 mV/decade and a limit of detection of 2.51 × 10−6 mol L−1 which is much improved as a result of diminishing ion fluxes in this solid contact ion-selective electrode. The present electrodes show clear selectivity for CIN from several inorganic, structurally related organic molecules, sugars, co-formulated drug, some common drug excipients and its degradation products. The results obtained by the proposed sensors were statistically analyzed and compared with those obtained by official method. No significant difference for either accuracy or precision was observed.

Integrated Gold-Thiol Based Potentiometric Sensors for In Situ Dual Drug-Protein Binding Studies on Naproxen/Diphenhydramine Salts Model

The diverse range of opportunities offered by ISEs has been broadly used in a number of pharmaceutical applications, with topics presented ranging from bioanalysis of drugs and metabolites, to green chemical analysis, impurity profiling, and drugs’ dissolution in biorelevant media. Attractively, solid-contact ISEs (SC-ISEs) have been implemented in many approaches due to their ability to offer stable and miniaturizable sensors. In this contribution, gold SC-ISEs were used in bare and thiol-doped forms for the analysis of the two co-formulated drugs namely, naproxen sodium and diphenhydramine hydrochloride in tablets. The unique ability of thiol to form a hydrophobic self-assembled monolayer on gold surface, resulted in more sensitive, stable, and drift-free potentiometric signals. The special advantages offered by the gold-thiol electrodes empowered us to utilize them as real-time analyzers to investigate the protein-binding behavior of the studied drugs by continuous in-situ monitoring of the drug in presence of serum albumin. The proposed sensors could offer a prediction of the pharmacokinetics of each component drug, giving the healthcare professionals the opportunity to provide a personalized medicine for the patients according to their different protein-binding characteristics.

Carbon Nanotubes Modified Electrode for Enhanced Voltammetric Sensing of Mebeverine Hydrochloride in Formulations and Human Serum Samples

Functionalized multi-walled carbon nanotubes (f-MWCNT) with open ends, small diameters and functional groups at defect sites along their sidewalls were obtained by simple acid oxidation of pristine MWCNTs. The carboxylic acid functionalization of MWCNTs was confirmed using FTIR spectroscopy. f-MWCNTs show a considerably higher BET surface area with respect to pristine MWCNTs. Mebeverine Hydrochloride (MV.HCl) was determined based on functionalized multi-wall carbon nanotubes modified carbon paste electrode (f-MWCNT/CPE) as a sensor. The electrochemical properties of the modified CPEs were characterized using electrochemical impedance spectra (EIS), scan electron microscopy (SEM), and cyclic voltammetry. The modified electrode exhibited higher electrocatalytic activities toward determination of MV.HCl. f-MWCNTs lead to enrichment the electrode surface properties and decreases the charge transfer resistances of the modified electrode facilitating the electron transfer process. The modified electrode was successfully applied for trace determination of MV.HCl in different pharmaceutical preparations; “Coloverin A”, “Colona” and “Colofac” tablets without interferences from excipients and co-formulated drugs. The achieved detection limit in human serum was 2.0 × 10−10 M. The described adsorptive anodic stripping voltammetric method is reliable, simple and sensitive enough for assay of MV. HCl in real plasma samples, pharmacokinetic studies, quality control and assurance of the drug in industry and in clinical laboratories.

Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study.

PurposeTenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF.Materials and MethodsWe prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years. Urine N-acetyl-β-D-glucosaminidase (NAG) and plasma cystatin-C were measured using samples collected in the first year. Data on renal function were retrospectively collected on HIV-infected patients receiving first-line TDF (n=40) and in antiretroviral therapy (ART)-naïve patients (n=24) for 3 years. Renal function was evaluated as estimated glomerular filtration rate (eGFR) from serum creatinine [Modification of Diet in Renal Disease (MDRD)] and cystatin-C.ResultsThe eGFR (cystatin-C) showed significant changes from 0 to 48 wks (p=0.002), with the lowest levels at 24 wks (84.3±18.8 mL/min vs. 90.3±22.5 mL/min, p=0.021 by post hoc test). Urine NAG levels did not differ at 0, 12, 24, and 48 wks, although eGFR (MDRD) significantly decreased from 0 (98.7±18.9 mL/min/1.73 m2) to 144 wks (89.0±14.7 mL/min/1.73 m2) (p=0.010). The first-line TDF group had significantly lower eGFR (MDRD) than the ART-naïve group at 144 wks (89.7 mL/min/1.73 m2 vs. 98.4 mL/min/1.73 m2, p=0.036). Thirteen (26%) participants experienced a decrease in renal impairment of 10 mL/min/1.73 m2 in eGFR (MDRD) at 144 wks.ConclusionThese data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF.

Micelle-enhanced spectrofluorimetric method for quantification of entacapone in tablets and human plasma.

In this paper, a simple and highly sensitive spectrofluorimetric method was developed and validated for the determination of entacapone (ETC). The proposed method is based on forming a highly fluorescent product through the reduction of ETC with Zn/HCl. The produced fluorophore exhibits strong fluorescence at λem 345nm after excitation at λex 240nm. The use of fluorescence enhancers such as Tween-80 and carboxy methyl cellulose (CMC) greatly enhanced the fluorescence of the produced fluorophore by 150% and 200%, respectively. Calibration curves showed good linear regression (r2>0.9998) within test ranges of 0.05-2.0 and 0.02-1.80μgmL-1 with lower detection limits of 1.27×10-2 and 4.8×10-3 μgmL-1 and lower quantification limits of 4.21×10-2 and 1.61×10-2 μgmL-1 upon using Tween-80 and or CMC, respectively. The method was successfully applied to the analysis of ETC in its pharmaceutical formulations (either alone or in presence of other co-formulated drugs). The results were in good agreement with those obtained using the official method. The methods were further extended to determine the drug in human plasma samples, and to study the pharmacokinetics of ETC. The paper is the first report on the spectrofluorimetric determination of entacapone.