Stability–Indicating Spectrofluorimetric Methods for the Determination of Metolazone and Xipamide in Their Tablets. Application to Content Uniformity Testing

A highly sensitive, simple and rapid stability-indicating spectrofluorimetric method was developed for the determination of metolazone (MET) and xipamide (XPM) in their tablets. The proposed method is based on the measurement of the native fluorescence of MET in methanol at 437 nm after excitation at 238 nm and XPM in alkaline methanolic solution at 400 nm after excitation at 255 nm. The fluorescence–concentration plots were rectilinear over the range of 2.0– 20.0 ng/mL for MET and 0.2– 2.0 μg/mL for XPM, with lower detection limits (LOD) of 0.35 ng/mL and 0.02 μg/mL and a lower quantification limit (LOQ) of 1.05 ng/mL and 0.07 μg/mL for MET and XPM, respectively. The method was successfully applied to the analysis of MET and XPM in their commercial tablets and the results were in good agreement with those obtained using the official and comparison methods, respectively. Furthermore, content uniformity testing of the studied pharmaceutical tablets was also conducted. The application of the proposed method was extended to stability studies of MET and XPM after exposure to different forced degradation conditions, such as acidic, alkaline, oxidative and photolytic degradation conditions, according to ICH Guidelines. Moreover, the method was utilized to investigate the kinetics of the alkaline, acidic and photolytic degradation of MET. The apparent first-order rate constants and half-life times were calculated. Proposals for the degradation pathways for both MET and XPM were postulated.     

Selectivity Improvement for Spectrofluorimetric Determination of Oseltamivir Phosphate in Human Plasma and in the Presence of Its Degradation Product

A simple and sensitive spectrofluorimetric method has been developed and validated for determination of oseltamivir phosphate (OSP). The proposed method is based on condensation reaction of the primary amino group of OSP with ninhydrin and phenylacetaldehyde in buffered medium (pH 6.5). The formed yellow fluorescent product exhibits excitation and emission maxima at 390 and 460 nm, respectively. The selectivity improvement of our proposed method is based on the water insolubility of the oseltamivir carboxylic acid (OSC) the active metabolite of OSP, which contains the same primary amino group as OSP but cannot, condensed with ninhydrin and phenylacetaldehyde reagents. The different experimental parameters affecting the formation and stability of the reaction product were carefully studied and optimized. The fluorescence intensity concentration plot is rectilinear in the range of 2–15 μg ml^?1 with detection and quantitation limits of 0.32 and 0.98 μg ml^?1, respectively. The proposed method was successfully applied for determination of OSP in commercial capsules, suspension and spiked human plasma with good percentage recovery. In addition, the developed procedure was extended to study the stability of OSP under different stress conditions; including acid and alkali hydrolysis, oxidation, photolysis, and thermal degradation. Furthermore, the kinetic of alkaline and acidic degradation of the cited drug were investigated. The apparent first order degradation rate constants were 0.258 and 0.318 K h^?1 with half times of 2.68 and 2.17 h, for acidic and alkaline degradation, respectively.     

Study on the Fluorescence Quenching Reaction of Amitriptyline and Clomipramine Hydrochlorides with Eosin Y and its Analytical Application

Amitriptyline.HCl (AMI) and clomipramine.HCl (CMI) react with eosin Y (EY) in pH 3.8 NaAc-AcH buffer solution to form ion association complex which results in quenching of fluorescence of EY and appearance of a new resonance Rayleigh scattering (RSS) spectrum at 620 nm. The spectral characteristics of absorption, fluorescence and RSS spectra have been investigated. The factors influencing the reaction were studied and optimum conditions for the reaction have been determined. Based on fluorescence quenching, a simple and sensitive spectrofluorimetric method for determination of AMI and CMI has been developed. The fluorescence quenching intensity was measured at 550 nm using an excitation wavelength of 310 nm. The calibration graph was found to be rectilinear in the range 0.08–2.0 μg?mL^?1 with detection limit of 0.017 μg?mL^?1 for AMI and 0.06–2.0 μg?mL^?1 with detection limit of 0.015 μg?mL^?1 for CMI. The method can be satisfactorily applied to the determination of AMI and CMI in tablets without interference from commonly occurring exicipients. The recovery and RSD values obtained indicate good accuracy and precision of the method. The mechanism of the reaction and fluorescence quenching has also been discussed.     

Micelle-Enhanced Spectrofluorimetric Method for Determination of Cyproheptadine Hydrochloride in Tablets: Application to In-Vitro Drug Release and Content Uniformity Test

A highly sensitive and simple spectrofluorimetric method was developed for the determination of cyproheptadine hydrochloride (CYP) in its pharmaceutical formulations. The proposed method is based on the investigation of the fluorescence spectral behaviour of CYP in a sodium dodecyl sulphate (SDS) micellar system. In aqueous solution, the fluorescence intensity of CYP was greatly enhanced (150 %) in the presence of SDS. The fluorescence intensity was measured at 410 nm after excitation at 280 nm. The fluorescence–concentration plot was rectilinear over the range 0.2–2.0 μg/mL, with lower detection limit of 0.06 μg/mL. The proposed method was successfully applied to the assay of commercial tablets as well as content uniformity testing. The application of the proposed method was extended to test the in-vitro drug release of CYP tablets, according to USP guidelines. The results were statistically compared with those obtained by official USP method and were found to be in good agreement.     

Stability-Indicating Spectrofluorimetric Method for the Assay of Ziprasidone in Capsules

A simple, rapid and highly sensitive spectrofluorimetric method was developed for determination of ziprasidone hydrochloride (ZPS) in capsules. The method is based on measuring the native fluorescence of ZPS in acetate buffer of pH 4.5 at 398 nm after excitation at 315 nm. The fluorescence-concentration plot was rectilinear over the range of 0.05–0.80 μg mL⁻¹ with a lower detection limit (LOD) of 6.0 ng mL⁻¹ and quantification limit (LOQ) of 20.0 ng mL⁻¹. The method was fully validated and successfully applied to the determination of ZPS in its capsules with average percentage recovery of 99.7 ± 1.4. The method was extended to stability study of ZPS. The drug was exposed to acidic, alkaline, oxidative and photolytic degradation according to ICH guidelines. Moreover, the method was utilized to investigate the kinetics of the alkaline, acidic and oxidative degradation of the drug. A proposal for the degradation pathways was postulated.     

Sensitive voltammetric determination of cysteamine using promazine hydrochloride as a mediator and modified multi-wall carbon nanotubes carbon paste electrodes

This paper presents a sensitive electrochemical method for the determination of cysteamine (CA) using promazine hydrochloride-modified multi-wall carbon nanotubes carbon paste electrode (PrH/MWCNTs CPE). Because of the good electrochemical activity of MWCNTs and the acceptable performance of promazine hydrochloride (PrH) as an electrocatalytic mediator, the modified electrode significantly enhanced the sensitivity for the detection of CA in comparison to the bare carbon paste electrode (CPE). All chemical parameters such as pH of solution, concentration of PrH and kinetic parameters of the system were investigated. Linear sweep voltammetric (LSV) method was used to follow the electrocatalytic effect of CA on the current–potential response of PrH. Under optimum conditions, the obtained net peak current ?I _p(I _sample???I _blank) was linear with CA concentrations in two dynamic ranges of 2.0–346.5 μmol l^?1 (?I _p?=?(0.0195?±?0.0043)C _CA?+?(0.7648?±?0.0397) (r ²?=?0.9948)) and 346.5–1,912.5 μmol l^?1 (?I _p?=?(0.0100?±?0.0026)C _CA?+?(3.8981?±?0.0828) (r ²?=?0.9911)) with a detection limit of 0.8 μmol l^?1. Finally, the PrH/MWCNTs CPE was successfully applied for the determination of CA in urine and drug samples with satisfactory results.     

Binding Study of Phenformin with Bovine Serum Album Using a Combined Technique of Equilibrium Dialysis with Flow-Injection Chemiluminescence Detection

ABSTRACT

The interaction between phenformin hydrochloride and bovine serum albumin (BSA) was investigated by the methods of chemiluminescence combined with equilibrium dialysis technique. A novel N-bromosuccinimide (NBS)–eosin Y (EY) chemiluminescence (CL) method was established for the determination of phenformin. The mechanism of this chemiluminescence system was proposed. Optimization studies were performed to determine the phenformin. Under the optimal conditions, the CL intensity was linear for a phenformin concentration over the range of 4.6 × 10^?8 to 5.0 × 10^?5 g/mL. The detection limit was 1.5 × 10^?8 g/mL. The data obtained by the present equilibrium dialysis–CL system were analyzed using the Klotz plot and the Scatchard analysis. The results showed that the Klotz plot and the Scatchard plot are linear with good correlation coefficient, indicating that the phenformin has only one type of binding site on BSA. The binding parameters were the number of the binding sites n (1.02) and the estimated association constant K (2.66 × 10⁴ L/mol). The chemiluminescence system combined with equilibrium dialysis developed in this work demonstrated its use for determination of interaction between drug and protein by using relatively simple instrument.     

Selective Spectrofluorimetric Method with Enhanced Sensitivity for Determination of Silodosine in Dosage Form and Human Plasma. Application to Stability Studies and Content Uniformity Testing

A novel, sensitive and selective spectrofluorimetric method has been developed and validated for determination of silodosine (SLD) in its dosage form and human plasma. The method is based on nucleophilic substitution reaction of SLD with 5-(dimethylamino) naphthalene-1-sulfonyl chloride (dansyl chloride) in presence of 5.0 × 10^?4 M sodium carbonate (pH 10.50) to yield a highly fluorescent derivative that was measured at 435 nm after excitation at 347 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence-concentration plot was rectilinear over the range 30.0–200.0 ng ml^?1, with a correlation coefficient of 0.9979. The limits of detection (LOD) and quantification (LOQ) were found to be 5.44 and 16.47 ng ml^?1, respectively. The proposed method was validated according to ICH guidelines, and successfully applied to the assay of commercial capsules as well as content uniformity testing. The high sensitivity of the proposed method allowed its successful application to the analysis of SLD in spiked human plasma with % recovery of 92.88 ± 1.05–100.73 ± 0.75%, (n = 6). The application of the proposed method was further extended to stability studies of SLD after exposure to different forced degradation conditions, such as acidic, alkaline and oxidative conditions, according to ICH guidelines, where this work describe the first attempt for selective spectrofluorimetric determination of silodosine in plasma and in the presence of its oxidative degradation.     

A Validated Spectrofluorimetric Method for the Determination of Citalopram in Bulk and Pharmaceutical Preparations Based on the Measurement of the Silver Nanoparticles-Enhanced Fluorescence of Citalopram/Terbium Complexes

A simple, sensitive, and accurate spectrofluorimetric method was developed for the determination of citalopram in bulk and pharmaceutical preparations. The method is based on the enhancement of the weak fluorescence signal (FL) of the Tb (III)-citalopram system in the presence of silver nanoparticles. Fluorescence intensities were measured at 555 nm after excitation at 281 nm. Prepared silver nanoparticles (AgNPs) were characterized by UV-Visible spectra and transmission electron microscopy (TEM). Various factors affecting the formation of citalopram-Tb (III)-AgNPs complexes were studied and optimized. The fluorescence intensity versus concentration plot was linear over the range 0.02–14 μg?mL^?1, with an excellent correlation coefficient of 0.9978. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 7.15?×?10^?6?μg?mL^?1 and 2.38?×?10^?5?μg?mL^?1 respectively. The proposed method was found to have good reproducibility with a relative standard deviation of 3.66 % (n?=?6). The interference effects of common excipients found in pharmaceutical preparations were studied. The developed method was validated statistically by performing recoveries studies and successfully applied for the assay of citalopram in bulk powder and pharmaceutical preparations. Percent recoveries were found to range from 98.98 % to 100.97 % for bulk powder and from 96.57 % to 101.77 % for pharmaceutical preparations.     

Micelle-Enhanced Spectrofluorimetric Method for Determination of Cholesterol-Reducing Drug Ezetimibe in Dosage Forms

A simple and sensitive spectrofluorimetric method was developed for the determination of ezetimibe in its pharmaceutical formulations. The proposed method is based on investigation of the fluorescence spectral behavior of ezetimibe in sodium dodecyl sulfate (SDS) micellar system. In aqueous solution of acetate buffer pH 5.0, the fluorescence intensity of ezetimibe was greatly enhanced, 200% enhancement, in the presence of SDS. The fluorescence intensity of ezetimibe was measured at 380 nm after excitation at 268 nm. The fluorescence-concentration plot was rectilinear over the range of 0.03–3.0 μg/mL with lower detection limit of 3.08 × 10⁻³ μg/mL. The method was successfully applied to the analysis of ezetimibe in its commercial tablets; the results were in good agreement with those obtained with the reported method. The application of the proposed method was extended to the stability studies of ezetimibe after exposure to different forced degradation conditions, such as acidic, alkaline, photo and oxidative conditions, according to ICH guidelines.     

Second-Derivative Synchronous Fluorescence Spectroscopy for the Simultaneous Determination of Fluphenazine Hydrochloride and Nortriptyline Hydrochloride in Pharmaceutical Preparations

A rapid, simple, and highly sensitive second-derivative synchronous fluorimetric (SDSF) method has been developed for the simultaneous analysis of binary mixtures of fluphenazine hydrochloride (FLZ) and nortriptyline hydrochloride (NTP) in their co-formulated tablets. The method is based upon measurement of the native fluorescence of these drugs at constant wavelength difference (Δλ)?=?120 nm in acetic acid. The different experimental parameters affecting the fluorescence intensity of the studied drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the range of 0.25–3.0 and 1–10 μg/ml for FLZ and NTP respectively, with lower detection limits (LOD) of 0.05 and 0.18 μg/ml and quantitation limits of 0.15 and 0.53 μg/ml for FLZ and NTP respectively. The proposed method was successfully applied for the determination of the studied compounds in their synthetic mixtures and in commercial co-formulated tablets. The results obtained were in good agreement with those obtained by the reference methods.     

Evaluation of carbon-supported copper phthalocyanine (CuPc/C) as a cathode catalyst for fuel cells using Nafion as an electrolyte

Carbon-supported copper phthalocyanine (CuPc/C) nanoclusters, as a novel suitable cathode catalyst in polymer electrolyte membrane fuel cells, have been synthesized via a combined solvent impregnation and milling procedure along with high-temperature treatment. For optimizing the electrocatalytic activity of the catalyst obtained, the electrode with varying Nafion ionomer contents in the catalyst layer was screened by cyclic voltammetry and linear sweep voltammetry employing a rotating disk electrode technique to investigate the effect of Nafion ionomer as for alkaline electrolyte. For comparative purposes, electrode with various contents of available anion-ionomer was also investigated. The results revealed that the content of Nafion ionomer can affect the oxygen reduction reaction activity of the CuPc/C catalyst and an optimal content of Nafion ionomer was around 3.5?×?10¹?μg?cm^?2, which corresponds well with the electrode prepared using available anion-ionomer. The electrode prepared using Nafion ionomer can produce a comparable performance to that of using available anion-ionomer, giving an onset potential at 0.1 V with a half-wave potential of ?0.03 V. Furthermore, Koutechy–Levich analysis showed that the value of electron transfer number is in the range of 3.40 to 3.74 when using electrode with varying Nafion ionomer contents from 2.5?×?10¹ to 1.6?×?10²?μg?cm^?2. The membrane electrode assembly fabricated with the CuPc/C cathode catalyst with a loading of 3.6 mg?cm^?2 and a Nafion membrane immersed in 3 M KOH for 48 h produced a power density of 3.8 mW?cm^?2 at room temperature.     

Stability-Indicating Method for the Determination of Meloxicam and Tetracaine Hydrochloride in the Presence of their Degradation Products

Abstract

Sensitive, spectrophotometric and densitometric methdos are described for the determination of meloxicam I and tetracaine hydrochloride II in the presence of their degradation products.

Meloxicam was determined in the presence of its degradation products (5-methyl-2-aminothiazole) III and benzothiazine carboxylic acid IV by two methods. These methods are the first derivative Spectrophotometry at 338 nm and TLC densitometric method at 365nm. The methods were applicable over the concentration range of 5–20μg.m^?1 and 2–10μg with mean accuracies of 99.66±0.91% and 99.99±0.70% respectively.     

A sensitive amperometric detection of dopamine agonist drug pramipexole at functionalized multi-walled carbon nanotubes (f-MWCNTs) modified electrode

The electrochemical detection of dopaminergic agonist drug pramipexole dihydrochloride monohydrate (PPX) has been investigated by cyclic voltammetric (CV) and amperometric i–t techniques at functionalized multi-walled carbon nanotubes-modified glassy carbon electrode. For the first time, a sensitive and rapid electrochemical method was developed for the determination of PPX. The surface morphological characteristics of the proposed electrode have been studied by using transmission electron microscopy (TEM); further, electrochemical impedance spectroscopy (EIS) and Fourier transform infrared spectroscopy (FTIR) have been employed. PPX shows an irreversible anodic peak, which may be ascribed to the oxidation of the –NH groups of PPX. The proposed method was showing good sensitivity of 0.993 μA μM^?1 cm^?2 with a linear range of 5 to 340 μM by amperometric i–t and CV technique shows a linear range of 12.5 to 313 μM with a sensitivity of 1.92 μA μM^?1 cm^?2. The recovery of PPX from blood serum samples was found 100.6 and 98.9 %, respectively. Furthermore, the proposed method has been demonstrated for the determination of PPX in commercially available pharmaceutical samples and good agreement of results obtained.     

Flow Injection Analysis of Pharmaceutical Compounds. VI. Determination of Some Central Nervous System Acting Drugs by UV-Spectrophotometric Detection

Abstract

The Present work describes a direct flow injection analysis (FIA) of five commonly used central nervous system (CNS) acting drugs namely amitriptyline hydrochloride, carbamazepine, clomipramine hydrochloride, fluphenazine hydrochloride and imipramine hydrochloride. The characteristics of the system and the conditions of the speatrophotometric determination are evaluated. The proposed technique can be applied for pharmaceutical quality control of the pure material and pharmaceutical dosage forms containing the drug. Amount ranging from 16 to 80 μg. ml^?1 of amitriptyline hydrochloride.

The Present work describes a direct flow injection analysis (FIA) of five commonly used central nervous system (CNS) acting drugs namely amitriptyline hydrochloride, carbamazepine, clomipramine hydrochloride, fluphenazine hydrochloride and imipramine hydrochlorode. The characteristics of the system and the conditions of the spectrophotometric determination are evaluated. The proposed technique can be applied for pharmaceutical quality control of the pure material and pharmaceutical dosage forms containing the drug. Amount ranging from 16 to 80 μ.ml^?1 of amitriptyline hydrochloride, carbamazepine and fluphenazine hydrochloride and from 32 to 160 μ. ml^?1 of clomipramine hydrochloride and imipramine hydrochloride dissolved and/or extracted in ethanol could be accurately analyzed. Standard addition (0.5 to 3 times of the claimed amounts) of authentic samples to powdered tablets gave good mean percent recoveries with low standard deviations. Samples can be introduced at rates of about 180 per hour or even more. The results obtained by applying the proposed FIA method are statistically analyzed and compared with those obtained from applying pharmacopoeial procedures.     

Spectrofluorimetric Determination of Terbinafine Hydrochloride and Linezolid in their Dosage Forms and Human Plasma

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of Terbinafine HCl (TRH) and linezolid (LNZ) in their pharmaceutical formulations. The proposed method is based on measuring the native fluorescence of the studied drugs in water at 336 nm after excitation at 275 nm for TRH and 375 nm after excitation at 254 nm for LNZ. The fluorescence–concentration plots were rectilinear over the range of 0.02–0.15 μg/mL for TRH and 0.5–5.0 μg/mL for LNZ. With lower detection limits of 3.0 and 110.0 ng/mL and a lower quantification limit of 9.0 and 320.0 ng/mL for TRH and LNZ, respectively. The method was successfully applied to the analysis of TRH in its commercial tablets, cream, gel and spray formulations and the results were in good agreement with those obtained with the official method. In addition the method was also applied to the analysis of LNZ in its capsule and I.V solution and the results were in good agreement with those obtained with the comparison method. The effect of sensitizers was studied. The method was extended to the determination of the studied drugs in spiked human plasma and the results were satisfactory.     

Sensitive Fluorescence Detection of Etimicin Based on Derivatives of Formaldehyde and Acetylacetone

A novel fluorescence method for the determination of etimicin is described. Etimicin reacts with acetylacetone and formaldehyde in pH 4.0 Britton-Robinson (B.R.) buffer solution to from a fluorescent substance [I]. Emission spectra of [I] and the reagent blank were overlapped, so the arithmetic emission spectra of the fluorescent substance were obtained by subtracted form the spectra of [I] to the spectra of the reagent blank using the Fluorescence Data Software. There is a linear relationship between the intensity of the arithmetic emission spectra and the concentration of etimicin. Effects of pH, amount of acetylacetone-formaldehyde, and heating time on the determination of etimicin have been examined. Etimicin can be determined over the concentration range of 1.0 to 10.0 μg?mL^?1 with a correlation coefficient of 0.9991. The relative standard deviation (RSD) for 11 repetitive determinations of 5.0 μg?mL^?1 etimicin is 0.22 %. The utility of this method was demonstrated by determining etimicin in commercial samples.     

HPLC测定盐酸二甲双胍肠溶片的含量

建立高效液相色谱法测定盐酸二甲双胍肠溶片含量的方法.采用Hypersil ODS2色谱柱(4.6mm×250mm,5μm),0.05％庚烷磺酸钠溶液(用10％磷酸溶液调节pH值至4.0)∶乙腈(84∶16)为流动相,紫外检测波长233nm;流速1.0mL/min;柱温为30℃.盐酸二甲双胍在0.11-10.70μg/m...     

Determination of Selenium (IV) in Natural Waters by HG‐AAS Using an Integrated Reaction Chamber Gas–Liquid Separator

Abstract

A simple online sequential insertion manifold coupled to a hydride generation atomic absorption spectrometer (HG‐AAS) has been developed for selective inorganic Se(IV) determination. The online method is based on the sequential insertion of sample and reagents in the integrated reaction chamber gas–liquid separator (RC‐GLS), which operates initially as reaction chamber for various sample volumes (up to 20 mL) and subsequently as gas–liquid separator with limited dead volume. The generated hydride from a large sample volume is trapped in the RC‐GLS for a short time and then it is flashed in the atomic absorption cell. The HCl and the NaBH₄ concentration was optimized for selective inorganic Se(IV) determination. For 8‐mL and 16‐mL sample consumption, the sampling frequency is 40 h^?1 and 24 h^?1, while the detection limit is 0.04 µg L^?1 and 0.03 µg L^?1, respectively. The precision (relative standard deviation) for 2.0 µg L^?1 Se(IV) (n=10) is 2.6% and 2.8% for 8 mL and 16 mL sample volumes, respectively. The accuracy of the proposed method was evaluated by analyzing the certified reference material, NIST CRM 1643d, and also by analyzing spiked natural water.     

Multipumping Nitrite Determination in Exhaled Breath Condensate

Abstract

A flow system based on multicommutation is proposed for the rapid, clean, and inexpensive determination of nitrites in small volumes of breath condensates. The procedure exploits the colorimetric detection of nitrite with the Griess reagent [0.03% naphthylethylene diamine dihydrochloride (NED), 0.5% sulpfhanilamide, and 3.0% phosphoric acid] in acidic medium at 540 nm correcting the variations of the baseline with measurements at 424 nm. The flow system was designed with a set of solenoid micropumps to minimize sample and reagent consumption and waste generation. The detection limit was estimated as 3.8 ng mL^?1 (99.7% confidence level) with a linear response ranging up to 500 ng mL^?1. The coefficient of variation was estimated as 0.7% for a solution containing 300 ng mL^?1 nitrite (n=9). Approximately 144 determinations can be carried out per hour, consuming only 678.4 µg Griess reagent and generating 1.184 mL of effluent per determination, thus providing an environmentally friendly alternative and a nonexpensive method. The procedure was successfully applied to determine nitrite in breath condensates.