Drugs In Pharmaceutical Preparations Research Articles

A Simple, Efficient and Ultrasensitive Gold Nanourchin Based Electrochemical Sensor for the Determination of an Antimalarial Drug: Mefloquine

AbstractMefloquine (MQ) is a quinoline based antimalarial drug, which is potent against multiple drug‐resistant Plasmodium falciparum. It is widely prescribed for the prophylactic treatment of malaria. Due to extensive usage of MQ, constant monitoring of the drug level in human body is of paramount importancein order to ensure that optimum drug exposure is achieved. The present work describes a gold nanourchins (AuNUs) based electrochemical sensor for the determination of MQ.AuNUs were synthesized via seed‐mediated method and characterized using ultraviolet‐visible spectroscopy, energy‐dispersive X‐ray spectroscopy, field emission scanning electron microscopy, zeta‐sizer and electrochemical techniques (electrochemical impedance spectroscopy and cyclic voltammetry). Fabrication of the sensor was done by drop‐coating the synthesized AuNUs onto a glassy carbon electrode. The fabricated sensor exhibited enhanced voltammetric response, which was attributed to the excellent conductivity and high surface area of AuNUs. Under optimum square wave voltammetric conditions, the sensor displayed two linear response ranges (from 2.0×10−9 to 1.0×10−6 M and from 1.0×10−6 to 1.0×10−3 M) with a detection limit of 1.4 nM. The electrode demonstrated good reproducibility, stability and selectivity over common interferents. The utility of the sensor was successfully assessed for quantification of the drug in pharmaceutical preparation and spiked human urine sample. Thus, the present study demonstrates a promising approach for determination of MQ with practical utility in quality control and clinical analysis.

Development of a Terbium-Sensitized Fluorescence Method for Analysis of Silibinin

Silibinin is a natural flavonoid with potent anticancer properties, as shown in both in vitro and in vivo experiments. Various methods have been used for silibinin analysis. Terbium-sensitized fluorescence methods have been widely used for the determination of drugs in pharmaceutical preparations and biological samples in recent years. The present work is aimed at providing a simple analytical method for the quantitative determination of silibinin in aqueous solutions based on the formation of a fluorescent complex with terbium ion. Terbium concentration, pH, and volume of buffer, the important effective parameters for the determination of silibinin by the proposed method, were optimized using response surface methodology. The fluorescence intensity of silibinin was measured at 545 nm using λex = 334 nm. The developed method was applied for the determination of silibinin in plasma samples after protein precipitation with acetone. Under optimum conditions, the method provided a linear range between 0.10 and 0.50 mg/L, with a coefficient of determination (R2) of 0.997. The LOD and LOQ were 0.034 and 0.112 mg/L, respectively. These results indicate that the developed method is a simple, low-cost, and suitable analytical method for the quantification of silibinin in aqueous solution and plasma samples.

From mercury to nanosensors: Past, present and the future perspective of electrochemistry in pharmaceutical and biomedical analysis

Polarography was the first developed automated method of voltage-controlled electrolysis with dropping mercury electrode (DME). Then, hanging mercury drop and static mercury drop electrodes were added as an alternative indicator electrode. In this way, polarography turned formally into voltammetry with mercury electrodes in the electroreduction way. Solid electrodes such as noble metal and carbon based electrodes can be used for the investigation of the compounds for both oxidation and reduction directions, which is called voltammetry. The voltammetric and polarographic techniques are more sensitive, reproducible, and easily used electroanalytical methods that can be alternative to more frequently used separation and spectrometric methods. Furthermore, in some cases there is a relationship between voltammetry and pharmaceutical samples, and the knowledge of the mechanism of their electrode reactions can give a useful clue in elucidation of the mechanism of their interaction with living cells. The voltammetric and polarographic analysis of drugs in pharmaceutical preparations are by far the most common use of electrochemistry for analytical pharmaceutical problems. Recent trends and challenges in the electrochemical methods for the detection of DNA hybridization and pathogens are available. Low cost, small sample requirement and possibility of miniaturization justifies their increasing development.

Synthesis of Ibuprofen-Molecularly Imprinted Polymers Used as Sensors to Determine Drug in Pharmaceutical Preparations

Synthesis of Ibuprofen-Molecularly Imprinted Polymers Used as Sensors to Determine Drug in Pharmaceutical Preparations

Development and validation spectroscopic methods for the determination of lomefloxacin in bulk and pharmaceutical formulations

Four simple, sensitive spectrophotometric and spectrofluorimetric methods (A-D) for the determination of antibacterial drug lomefloxacin (LMFX) in pharmaceutical formulations have been developed. Method A is based on formation of ternary complex between Pd(II), eosin and LMFX in the presence of methyl cellulose as surfactant and acetate-HCl buffer pH 4.0. Spectrophotometrically, under the optimum conditions, the ternary complex showed absorption maximum at 530 nm. Methods B and C are based on redox reaction between LMFX and KMnO4 in acid and alkaline media. In indirect spectrophotometry method B the drug solution is treated with a known excess of KMnO4 in H2SO4 medium and subsequent determination of unreacted oxidant by reacting it with safronine O in the same medium at λmax = 520 nm. Direct spectrophotometry method C involves treating the alkaline solution of LMFX with KMnO4 and measuring the bluish green product at 604 nm. Method D is based on the chelation of LMFX with Zr(IV) to produce fluorescent chelate. At the optimum reaction conditions, the drug-metal chelate showed excitation maxima at 280 nm and emission maxima at 443 nm. The optimum experimental parameters for the reactions have been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the selected drug in pharmaceutical preparations with good recoveries.

Development and application of a portable instrument for drugs analysis in pharmaceutical preparations

This article describes the application and performance of an inexpensive, simple and portable device for colorimetric quantitative determination of drugs in pharmaceutical preparations. The sensor is a light detector resistor (LDR) incorporated into a black PTFE cell and coupled to a low-cost multimeter (Ohmmeter). Quantitative studies were performed with captopril/p-chloranil/H2O2 and methyldopa/ammonium molybdate systems. Calibration curves were obtained by plotting the electrical resistance of the LDR against the concentration of the colored species in the ranges 1.84 × 10-4 to 1.29 × 10-3mol L-1 and 5.04 × 10-4 to 2.52 × 10-3 mol L-1 for captopril/p-chloranil/H2O2 and methyldopa/ammonium molybdate systems, respectively, exhibiting good coefficients of determination. Statistical analysis of the results obtained showed no significant difference between the proposed methodologies and the official reported methods, as evidenced by the t-test and variance ratio at a 95% confidence level. The results of this study demonstrate the applicability of the instrument for simple, accurate, precise, fast,in situ and low-cost colorimetric analysis of drugs in pharmaceutical products.

Spectrophotometric determination of Phenylephrine hydrochloride and Salbutamol sulphate drugs in pharmaceutical preparations using diazotized Metoclopramide hydrochloride

A spectrophotometric method has been proposed for the determination of two drugs containing phenol group [phenylephrine hydrochloride (PHP) and salbutamol sulphate (SLB)] in pharmaceutical dosage forms. The method is based on the diazotization reaction of metoclopramide hydrochloride (MCP) and coupling of the diazotized reagent with drugs in alkaline medium to give intense orange colored product (?max at 470 nm for each of PHP and SLB). Variable parameters such as temperature, reaction time and concentration of the reactants have been analyzed and optimized. Under the proposed optimum condition, Beer’s law was obeyed in the concentration range of 1-32 and 1-14 ?g mL-1 for PHP and SLB, respectively. The limit of detection (LOD) and limit of quantification (LOQ) for each of PHP and SLB were 0.60, 0.52 ?g mL-1 and 2.02, 1.72 ?g mL-1, respectively. No interference was observed from common excipients present in pharmaceutical preparations. The good correlation coefficients and low relative standard deviation assert the applicability of this method. The suggested method was further applied for the determinations of drugs in commercial pharmaceutical preparations, which was compared statistically with reference methods by means of t- test and F- test and were found not to differ significantly at 95% confidence level. The procedure was characterized by its simplicity with accuracy and precision.

Spectrophotometric determination of Phenylephrine hydrochloride and Salbutamol sulphate drugs in pharmaceutical preparations using diazotized Metoclopramide hydrochloride

A spectrophotometric method has been proposed for the determination of two drugs containing phenol group [phenylephrine hydrochloride (PHP) and salbutamol sulphate (SLB)] in pharmaceutical dosage forms. The method is based on the diazotization reaction of metoclopramide hydrochloride (MCP) and coupling of the diazotized reagent with drugs in alkaline medium to give intense orange colored product (?max at 470 nm for each of PHP and SLB). Variable parameters such as temperature, reaction time and concentration of the reactants have been analyzed and optimized. Under the proposed optimum condition, Beer’s law was obeyed in the concentration range of 1-32 and 1-14 ?g mL-1 for PHP and SLB, respectively. The limit of detection (LOD) and limit of quantification (LOQ) for each of PHP and SLB were 0.60, 0.52 ?g mL-1 and 2.02, 1.72 ?g mL-1, respectively. No interference was observed from common excipients present in pharmaceutical preparations. The good correlation coefficients and low relative standard deviation assert the applicability of this method. The suggested method was further applied for the determinations of drugs in commercial pharmaceutical preparations, which was compared statistically with reference methods by means of t- test and F- test and were found not to differ significantly at 95% confidence level. The procedure was characterized by its simplicity with accuracy and precision.

Stability-Indicating Micellar LC Methods with Time-Programmed UV Detection for Determination of Three Oxicams in Pharmaceuticals with Direct Injection of Gel and Suppositories

Two stability-indicating micellar liquid chromatographic methods were developed and validated for the determination of three oxicams, namely piroxicam (PX), tenoxicam (TX), and lornoxicam (LX), in presence of their degradation product and potential impurity (2-aminopyridine, AP). The analyses were achieved using C8 column (150 mm × 4.6 mm i.d., 5 µm particle size). In Method I, a micellar mobile phase consisting of 0.15 M SDS, 10% n-propanol, 0.3% triethylamine, and 0.02 M orthophosphoric acid (pH 3.0) was used for simultaneous determination of PX, TX, and AP. In Method II, a mobile phase of the same composition but at pH 6.0 was used for separation of LX and AP. Time-programmed UV detection was applied to allow sensitive determination of the drugs and AP. Method I showed good linearity for PX, TX, and AP over the concentration ranges of 1.0–32.0, 1.0–20.0, and 0.5–10.0 µg/mL, respectively, while Method II was linear over the concentration ranges of 0.8–32.0 and 0.5–10.0 µg/mL for LX and AP, respectively. The developed methods were applied for quality control of the three drugs in pharmaceutical preparations including gel and suppositories with direct injection of samples. The proposed method agreed well with the concept of green chemistry.

Spectrophotometric and spectrofluorimetric determinations of veterinary drug enrofloxacin in pharmaceutical formulation

Four simple, sensitive spectrophotometric and spectroflourimetric methods (A-D) for the determination of veterinary drug enrofloxacin (ENFX) in pharmaceutical formulation have been developed. Method (A) is based on formation of ternary complex of ENFX with Pd(II) in presence of methyl cellulose as surfactant and acetate-HCl buffer pH 4.0. Method (B) is based on the oxidation of ENFX with alkaline potassium permanganate to give a green colored reaction product. The reaction was monitored spectrophotometrically by measuring the absorbance of the reaction product at 604 nm. Method (C) is based on the oxidation of the ENFX by a known excess of potassium permanganate in acid medium and subsequent determination of unreacted oxidant by reacting it with safronine O (SFO). Method (D) is based on the chelation of ENFX with Zr(IV), to produce fluorescent chelate. At the optimum reaction conditions, the drug/metal chelate showed excitation maxima at 280 nm and emission maxima at 440 nm. The optimum experimental parameters for the reaction have been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the selected drug in pharmaceutical preparations with good recoveries. The procedures were accurate, simple and suitable for quality control application.

Mixed micelle cloud point-magnetic dispersive μ-solid phase extraction of doxazosin and alfuzosin

Mixed micelle cloud point extraction (MM-CPE) combined with magnetic dispersive μ-solid phase extraction (MD-μ-SPE) has been developed as a new approach for the extraction of doxazosin (DOX) and alfuzosin (ALF) prior to fluorescence analysis. The mixed micelle anionic surfactant sodium dodecyl sulfate and non-ionic polyoxyethylene(7.5)nonylphenylether was used as the extraction solvent in MM-CPE, and diatomite bonding Fe3O4 magnetic nanoparticles were used as the adsorbent in MD-μ-SPE. The method was based on MM-CPE of DOX and ALF in the surfactant-rich phase. Magnetic materials were used to retrieve the surfactant-rich phase, which easily separated from the aqueous phase under magnetic field. At optimum conditions, a linear relationship between DOX and ALF was obtained in the range of 5–300ngmL−1, and the limits of detection were 0.21 and 0.16ngmL−1, respectively. The proposed method was successfully applied for the determination of the drugs in pharmaceutical preparations, urine samples, and plasma samples.

Excipient foods: designing food matrices that improve the oral bioavailability of pharmaceuticals and nutraceuticals.

The oral bioavailability of many lipophilic bioactive agents (pharmaceuticals and nutraceuticals) is limited due to various physicochemical and physiological processes: poor release from food or drug matrices; low solubility in gastrointestinal fluids; metabolism or chemical transformation within the gastrointestinal tract; low epithelium cell permeability. The bioavailability of these agents can be improved by specifically designing food matrices that control their release, solubilization, transport, metabolism, and absorption within the gastrointestinal tract. This article discusses the impact of food composition and structure on oral bioavailability, and how this knowledge can be used to design excipient foods for improving the oral bioavailability of lipophilic bioactives. Excipient foods contain ingredients or structures that may have no bioactivity themselves, but that are able to promote the bioactivity of co-ingested bioactives. These bioactives may be lipophilic drugs in pharmaceutical preparations (such as capsules, pills, or syrups) or nutraceuticals present within food matrices (such as natural or processed foods and beverages).

Simultaneous determination of sitagliptin and metformin in ternary mixture with sitagliptin acid degradation product

In this work, the acidic degradation product of sitagliptin phosphate monohydrate (STG) was synthesized, separated and its structure was elucidated. Additionally, two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of STG. The first method comprised the determination of STG in binary mixture with sitagliptin acid degradation product (SDP) in laboratory prepared mixtures, in plasma and in dosage form. This method was based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer (pH =4.6) - acetonitrile (30:70, v : v ) with fluorometric detection. The fluorometric detector was operated at 267 nm for excitation and 575 nm for emission. In the second method, the simultaneous determination of STG and metformin (MET) in the presence of SDP has been developed. In this method, the ternary mixture of STG, MET and SDP was separated using a mobile phase consisting of potassium dihydrogen phosphate buffer (pH = 4.6) - acetonitrile (15:85, v : v ) with UV detection at 220 nm. Chromatographic separation in the two methods was achieved on a Symmetry ® Waters C18 column (150 mm × 4.6 mm, 5 μm). The optimized methods were validated and proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparations.

Ion-Pair LC Method for Simultaneous Determination of Aliskiren Hemifumarate, Amlodipine Besylate and Hydrochlorothiazide in Pharmaceuticals

A rapid and precise LC method was developed for the simultaneous determination of aliskiren hemifumarate (ALS), amlodipine besylate (AML) and hydrochlorothiazide (HCZ) using acetonitrile:25 mM octane sulfonic acid sodium salt monohydrate in water (60:40 v/v) as the mobile phase. The flow rate was maintained at 1.2 mL min−1 on a stationary phase composed of Supelco, Discovery® HS (C18) column (25 cm × 4.6 mm, 5 μm). Isocratic elution was applied throughout the analysis. Detection was carried out at λ max (232 nm) at ambient temperature. The method was validated according to ICH guidelines. Linearity, accuracy and precision were satisfactory over the concentration ranges of 32–320, 2–44 and 4–64 μg mL−1 for ALS, AML and HCZ, respectively. LOD and LOQ were estimated and found to be 0.855 and 2.951 μg mL−1, respectively, for ALS, 0.061 and 0.202 μg mL−1, respectively, for AML as well as 0.052 and 0.174 μg mL−1, respectively, for HCZ. The method was successfully applied for the determination of the three drugs in their co-formulated tablets. The results were compared statistically with reference methods and no significant difference was found. The developed method is specific and accurate for the quality control and routine analysis of the cited drugs in pharmaceutical preparations.

English

A simple and highly selective method for determination of enalaprilat (ENT), lisinopril (LSP) and benazepril hydrochloride (BZP) in pharmaceutical dosage forms as well as spiked human plasma by ion chromatography with UV detection has been developed. ENT and LSP are compounds with little inherent hydrophobicity that make their analysis using HPLC essentially sophisticated necessitating either complex extraction procedures or especial detection methods. The method proposed is based upon ionization of those two drugs in basic medium to be well retained and readily resolved as dicarboxylic acid anions using IonPac AS11 (13 μm particle size, 4 × 250 mm, Dionex) anion exchange column adopting a very simple clean-up procedure via a single-step protein precipitation with UV detection at 215 nm. The three drugs were successfully determined in pharmaceutical dosage forms as well as in spiked human plasma with tyrosine as internal standard with a recovery approaching 100%. Adopting this proposed procedure, the analytes produce well shaped peaks with good linear relationship over the investigated concentration ranges and values of (r) higher than 0.998 for all drugs. ion level of200 ng ml-1 of the three drugs, therefore being satisfactory for their purposed analysis. The method was validated with respect to specificity, recovery, accuracy, precision and linearity. Moreover, the method could be applied to the determination of the drugs in pharmaceutical preparations. The method was validated with respect to specificity, recovery, accuracy, precision and linearity and the method proved applicable for routine fast analysis of the studied drugs. Key words: Benazepril, enalaprilat, lisinopril, ion chromatography, pharmaceutical, plasma.

Development of gradient HPLC-DAD method for assay of ternary mixture containing amebicide and analgesic drugs

Summary Validated gradient high-performance liquid chromatography-diode array detection (HPLC-DAD) method has been developed for simultaneous determination of diloxanide furoate (DIL), mebeverine hydrochloride (MBV), and metronidazole (MET) in their pharmaceutical preparation. This method was based on a reversed-phase HPLC separation of the cited drugs on a C-18 column (150 mm × 4.6 mm, 5 μm) with a gradient elution system of 0.05 M phosphate buffer with 1% (v/v) of triethylamine adjusted to pH 3.0-methanol as the mobile phase at the flow rate of 1.0 mL min−1. The separation was carried out at ambient temperature. Quantitation was achieved with DAD detection at 260 nm for DIL and MEB, and at 320 for MET based on peak area with linear calibration curves at concentration ranges 4–30, 1–20, and 1–30 μg mL−1 for DIL, MEB, and MET, respectively. The proposed chromatographic method was successfully applied to the determination of the investigated drugs in pharmaceutical preparation. It was validated in complian...

Comparative determination of miconazole, nystatin, hydrocortisone and neomycin by HPTLC/HPLC-DAD

Two new validated methods for the quantification of miconazole (MIC), nystatin (NYS), hydrocortisone acetate (HCA) and neomycin (NS) by high performance thin layer chromatography (HPTLC)-densitometry and reverse-phase high-performance liquid chromatography procedure coupled with photodiode array detector (RP-HPLC-DAD) were developed and compared. HPTLC separations were performed using a mobile phase, ethylacetate:methanol:glacial acetic acid (60:40:0.4, v : v : v ) for MIC, NYS, HCA and ethylacetate for NS. For HPLC-DAD analysis, using an isocratic elution system, separation of all compounds was achieved. Good resolution and quantization were achieved, accuracy and precision, as well as detection and quantitation limits of the two methods, were evaluated and compared. Excellent linearity was observed for all of the standard calibration curves, and the correlation coefficients were above 0.9997. HPTLC limits of quantitation were 15.37×10 -2 , 9.8×10 -2 , 13.32×10 -2 and 15.19×10 -2 µg/mL for MIC, NYS, HCA and NS respectively, whereas HPLC limits were 6.80×10 -2 , 6.56×10 -2 , 1×10 -1 and 10.16×10 -2 µg/band for MIC, NYS, HCA and NS respectively. In comparison with HPLC, HPTLC is less expensive and faster procedure, requiring 2-3 h to analyse 10-12 samples on a single plate. The developed methods were proved to be specific, robust and accurate for the determination of cited drugs in pharmaceutical preparations.

Validated Stability-Indicating Methods for the Simultaneous Determination of Amiloride Hydrochloride, Atenolol, and Chlorthalidone Using HPTLC and HPLC with Photodiode Array Detector

Two stability-indicating chromatographic methods are described for simultaneous determination of amiloride hydrochloride (AMI), atenolol (ATE), and chlorthalidone (CHL) in combined dosage forms. The first method was based on HPTLC separation of the three drugs followed by densitometric measurements of their bands at 274 nm. The separation was carried out on Merck HPTLC silica gel 60F254 aluminum sheets using chloroform-methanol-ammonia 27%, w/w (9 + 2 + 0.3, v/v/v) mobile phase. Analysis data was used for the linear regression graph in the range of 0.1-0.5, 0.8-5.0, and 0.3-1.5 microg/band for AMI, ATE, and CHL, respectively. The second method was based on an RP-HPLC separation of the cited drugs performed on an RP stainless steel C18 analytical column (250 x 4.6 mm id) with a gradient elution system of methanol and 0.05 M aqueous phosphate buffer adjusted to pH 4 as the mobile phase, at the flow rate of 1.0 mL/min. Quantitation was achieved with photodiode array detection at 275 nm for AMI and 225 nm for ATE and CHL. The calibration graphs for each drug were rectilinear in the range of 2-50, 25-150, and 2-100 microg/mL for AMI, ATE, and CHL, respectively. The proposed chromatographic methods were successfully applied for determination of the investigated drugs in pharmaceutical preparations. Both methods were validated in compliance with International Conference on Harmonization guidelines in terms of linearity, accuracy, precision, robustness, LOD, and LOQ.

Electrochemical Determination of b-Blocker Alprenolol Hydrochloride in Its Pharmaceutical Formulations

mol/L for electrodes (I) and (II) respectively. The constructed electrodes gave average selective precision and accuracy within the pH range (3-8). Interferences from common cations, alkaloids, sugars, amino acids and drug excipients were reported. The results obtained by the proposed electrodes were also applied successfully to the determination of the drug in pharmaceutical preparations.

Extractive Spectrophotometric Method for the Determination of Lamivudine and Zidovudine in Pharmaceutical Preparations Using Bromocresol Purple

A new spectrophotometric method has been established for the quantitation of lamivudine (LVD) and zidovudine (ZVD) in pharmaceutical preparations. The method is based on the reaction between the investigated drug substances and bromocresol purple (BCP) producing ion‐pair complexes in acidic buffers which are suitable for chloroform extraction. The maximum absorbance of these complexes was measured at 424 nm in chloroform. All variables were studied to optimize the reaction conditions. Linearity ranges were found to be 25–250 μg mL−1 for LVD‐BCP and 50–300 μg mL−1 for ZVD‐BCP. The developed method was successfully applied for the determination of these drugs in pharmaceutical preparations. Excipients in pharmaceutical formulations did not interfere in the analysis. The results were compared statistically with those obtained by the HPLC method reported in the literature. According to the results, the proposed method can be recommended for quality control and routine analysis.