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This work investigates the flow structure development due to the injecting water into the annulus of heavy oil pipe flow. Numerical simulation of the axisymmetric core-annular turbulent flow is carried out using the standard κ-ω model. The flow field and flow characteristics are investigated using FLUENT 6.3.26. The core-annular flow of heavy oils-water in 15.24 cm diameter pipe, with three core diameters is considered. The influence of flow parameters upon the development of axial and radial velocity, turbulent kinetic energy, turbulence intensity, and strain rate profiles are investigated. Results show that the flow development depends on the core to outer diameters ratio, oil viscosity, flow velocity, and water loading ratio. As oil's viscosity increases, the flow structure develops faster towards fully- developed one. Fully- developed velocity profiles show uniform distribution in oil's core, while all velocity changes occur in water flowing in pipe annulus. The flow in the core region seems to be as rigid body carried by annular water flow. It has been demonstrated that major changes in flow structure occur at the oil-water interface

Two green-sensitive spectrofluorometric methods were investigated for assay of rupatadine (RUP) [method I] and its binary mixture with montelukast (MKT) [method II]. Method I depends on measuring native fluorescence of RUP in the presence of 0.10 M H 2 SO 4 and 0.10%w/v sodium dodecyl sulfate at 455 nm after excitation at 277 nm. The range of the first method was 0.20–2.00 µg ml −1 with detection and quantitation limits of 59.00 and 179.00 ng ml −1 , respectively. Method II depends on the first derivative synchronous spectrofluorometry. The derivative intensities were measured for the two drugs in an aqueous solution containing Mcllvaine's buffer pH 2.60 at fixed Δ λ of 140 nm. Each drug was estimated at zero-contribution of the other. The intensity was measured at 261 and 371 nm for RUP and MKT, respectively. The method was linear over 0.10–4.00 and 0.20–1.60 µg ml −1 with limits of detection 31.00 and 66.00 ng ml −1 and limits of quantitation 94.00 and 200.00 ng ml −1 for RUP and MKT, respectively. The method was extended to determine this mixture in laboratory-prepared mixtures and combined tablets. Method validation was performed according to ICH guidelines. Statistical interpretation of data revealed good agreement with the comparison method. Method greenness was confirmed by applying three different assessment tools.

Green analysis has turned out to be of a great value in all areas, including pharmaceutical analysis. Thus, it is extremely important to consider the environmental influence of each step in developing any analysis technique. The present work illustrates a validated, simple and green spectrofluorimetric method for the analysis of dantrolene sodium (DAN). The developed process is characterized by being of high sensitivity as well as being relatively inexpensive. The suggested technique based on the formation of a highly fluorescent product of DAN via its reduction by the aid of Zn/HCl system. The resulting fluorophore showed a powerful fluorescence at λ em 344 nm after excitation at λ ex 279 nm. Calibration graph revealed a great linear regression ( r = 0.9998) within concentration ranging from 0.05 to 2.0 µg ml −1 . The suggested method had very low detection and quantification limits of 0.010 and 0.031 µg ml −1 , respectively. The applied technique was effectively used in the determination of DAN in its pharmaceutical preparations. The results were compared with those from using the official United States Pharmacopeia (USP) method and they were in a good agreement. Moreover, content uniformity testing of DAN in capsules was performed adopting the investigated technique with satisfying results. The greenness of the suggested technique was confirmed by the three standard assessment tools. Therefore, the developed technique can be used in the routine quality control analysis of DAN with minimum harmful impact on nature or individuals.

Curcumin is a natural product that is frequently utilized in cancer prevention and treatment. The significant benefit of vegetable-derived nutraceuticals in combination with widespread cytostatic medication such as ponatinib is to reduce toxicity and side effects. In this paper, we focus the study on analytical quantification of ponatinib and curcumin through highly sensitive synchronous spectrofluorometric method. Applying this method at Δλ = 160 nm, each of ponatinib and curcumin could be measured at 303 and 412 nm without interference from each others. The diverse experimental factors impacting the performance of the method were studied and optimized. The method exhibited a reasonable linearity in the ranges of 5.0–60.0 and 10.0–200.0 ng/mL for ponatinib and curcumin, respectively with detection limits of 1.48 and 1.22 ng/mL and quantitation limits of 4.49 and 3.68 ng/mL, respectively. The anticipated method was employed for the assessment and evaluation of the studied drugs in the spiked human plasma samples. The mean % recoveries in plasma samples (n = 6) for each of ponatinib and curcumin were 99.84 ± 1.86 and 100.06 ± 2.72, accordingly. The developed method was validated in conformity with the requirements of International Council of Harmonization (ICH).

We report the detection and quantification of important ulcerative colitis drugs olsalazine (OLS) and sulfasalazine (SUL) by the spectrofluorometric method. The proposed method was optimized and validated by using the quenching effect on the acriflavine fluorescence. The method was applied on the detection and quantification of OLS and SUL under optimized conditions showing the calibration curves were linear (range: 1.0–10.0 µg ml −1 ), with correlation coefficients R 2 of 0.9999 for both drugs. The limits of detection (LOD) and quantification (LOQ) were 53 and 104 ng ml −1 for the OLS and 160 and 315 ng ml −1 for the SUL. This method permitted the analysis of OLS and SUL in their pure and pharmaceutical forms. The proposed spectrofluorimetric method was also evaluated against ‘green’ criteria and all the experimental results make it an eco-friendly and safe method for the detection of OLS and SUL.

The growth of tumor tissue is extremely pervasive among post-menopausal women. Commonly, from the clinical application, adjuvant selective estrogen receptor modulators such as tamoxifen are prescribed for prohibiting metastatic breast cancer, while its analog, clomiphene, is used to treat infertility in women. Lately, the significance of green chemistry on our environment was through reducing the influence of hazardous chemicals. Consequently, efforts were screened to perform a fast and simple eco-friendly green method for the determination of two aromatase inhibitors. In this study, a sensitive green spectrofluorimetric approach was developed to detect and characterize tamoxifen citrate (TAM) and clomiphene citrate (CLO) via complex formation with erythrosine B. The reaction between erythrosine B dye (EB) and the two aromatase inhibitors results in quenching the fluorescence activity of the dye by the formation of ion-pair in Britton-Robinson buffer (BRB) solution (pH 4.3) at 554 nm (λex = 527 nm). The approach outcome confirmed that the solvent’s inherent nature has a critical impact on the approachs’ sensitivity and reproducibility. An approved linear correlation was achieved between the reduction in the emission value of EB’s fluorescence and the concentration in the ranges of 40.0–600.0 ng/mL for both TAM and CLO with mean % recoveries 100.20 ± 0.93 and 100.07 ± 1.09, respectively. The approach was validated regarding ICH protocols, and the outcomes were acceptable. The changes in Gibb’s free energy (ΔG°) by the obtained ion-pair between EB and TAM or CLO were −36.65 or −37.03 kJ mol−1, respectively, which indicates the reaction feasibility at ambient temperature. Commercial dosage forms for TAM and CLO were simply analyzed, and good recoveries were achieved within the range. The National Environmental Methods Index, Analytical Eco-Scale, and Green Analytical Procedure Index applications to our illustrated approach present additional eligibility to this study.

For the estimation of some co-administered antimicrobials, two highly accurate and precise spectrofluorimetric methods were developed. Fluconazole (FLZ) is co-administered with either ciprofloxacin (CPR) or ofloxacin (OFX) for the treatment of certain microbial infections. On the other hand, another antimicrobial drug, vancomycin (VNC) is co-administered with ciprofloxacin (CPR) for peritonitis treatment. In method I, conventional spectrofluorimetry has been introduced for the concurrent quantitative estimation of FLZ in presence of OFX or CPR. While in method II, a first derivative synchronous spectrofluorimetric technique was adapted for quantitation of VNC and CPR co-administered combination. Both of them were utilized for estimation of the considered drugs in raw materials, laboratory prepared mixtures, dosage forms, and biological fluids. Method I was relied on simultaneous measuring of the native fluorescence of FLZ and OFX or CPR without any overlapping between the emission spectra of each binary mixture (FLZ / OFX) and (FLZ / CPR). Fluorescence intensities were measured at 283.0, 483.0 and 436.0 nm after excitation at 262.0, 292.0 and 275.0 nm for FLZ, OFX and CPR, respectively. Method II was utilized the synchronous fluorescence intensity of VNC and CPR in methanol at Δλ = 40 nm. The first derivative synchronous spectra were calibrated at 297.0 nm for VNC and at 379.5 nm for CPR. Different variables influencing conventional and synchronous fluorescence intensities of the four antimicrobials under investigation were precisely optimized. Both methods were successfully investigated for the determination of the studied drugs in plasma. The linear data analysis for the calibration curves reveals a good relationship in the ranges of 1.0–10.0, 0.25–2.5 and 0.06–0.6 μg/mL for FLZ, OFX and CPR for method I with limits of detection 0.144, 0.038 and 0.007 μg/mL and limits of quantitation of 0.437, 0.114 and 0.021 μg/mL for FLZ, OFX and CPR, respectively. Linearity range for method II was 0.5 –10.0 μg/mL for VNC and CPR with detection limits of 0.127 and 0.110 μg/mL and quantitation limits of 0.380 and 0.334 μg/mL for VNC and CPR, respectively. International Council on Harmonization ICH Q2 (R1) Guidelines were followed in the developed methods validation. The achieved outcomes were statistically compared with those found by the reported ones, and no significant difference was observed.

In the present study, we conducted two facile and highly sensitive spectrofluorimetric approaches in order to quantify the vasoprotective agents; troxerutin (TROX) and calcium dobesilate (DOB) in the presence of hydroquinone (HQ) (as a highly toxic impurity and potential degradation product of DOB) in commercial formulations and human plasma. The first approach relies simply on using ethanol as an eco-friendly solvent for the estimation of DOB at 345 nm after being excited at 305 nm. The linearity was carefully investigated between DOB concentration and the relative fluorescence intensity in the range of 0.05–0.8 µg ml−1. Due to the high method simplicity and sensitivity, applying the first approach to quality control analysis and spiked human plasma samples with mean % recoveries 100.74 ± 3.71 adds another merit. The second approach involved rapid conventional fluorimetric estimation of ethanolic TROX solution in TROX/DOB combined dosage forms at 455/350 nm (emission/excitation) with a linear calibration chart covering the range of 0.1–1.2 µg ml−1. Moreover, the second approach involved a comprehensive study in a trial to solve the problem of superposition of DOB and HQ graph adopting the first derivative synchronous fluorimetric mechanism in ethanol at Δλ = 60 nm. Therefore, DOB was measured at 286 and 323 nm, while HQ could be quantitated at 301 nm. Beer's–Lambert law has complied over the ranges of 0.1–1.0 µg ml−1 and 0.02–0.4 µg ml−1 for DOB and HQ, respectively. Guidelines adopted by the International Council of Harmonization (ICH) were used to validate the target approaches. The developed methods are more convenient for routine quality control laboratory instead of the time-consuming and sophisticated reported techniques. Moreover, different aspects of evaluating the greenness of the proposed approaches were conducted to have a complete image of their environmental impact.

Four simple, rapid, accurate and precise spectrophotometric methods were established and validated in accordance with ICH Q2 (R1) guidelines for the simultaneous determination of Vancomycin (VNC) and Ciprofloxacin (CPR) in their raw materials, laboratory prepared mixtures and pharmaceutics. Method A depends on using first derivative spectrophotometry (D1) where VNC and CPR were resolved at 243.6 and 262.0 nm, respectively. Concerning method B, it is based on utilizing first derivative of ratio spectra (DD1) where determination was performed at the peak maxima at 244.0 nm and 258.0 nm for VNC and CPR, respectively. Two chemometric models were applied for the quantitative analysis of both drugs in their laboratory prepared mixtures, namely, partial least squares (PLS) (method C) and artificial neural network (ANN) (method D). For univariate methods linearity range for both drugs was in the range of 3–30 and 1–10 μg/mL for VNC and CPR, respectively. Multivariate calibration methods using five level, two factor calibration model for the development of 25 mixtures were also applied for the simultaneous estimation of the two drugs in their laboratory prepared mixture using spectral region from 200.0 to 300.0 nm using interval 1 nm. The suggested methods have been successfully extended to the assay of the two studied drugs in laboratory-prepared mixtures and pharmaceuticals with excellent recovery. First derivative spectrophotometry (D1) was also applied for the assay of both analytes in spiked human plasma with good recovery. No interaction with common pharmaceutical additives has been observed which indicate the selectivity of the method. The results obtained were favourably compared with those obtained applying the reported methods. The methods are validated in compliance with the ICH Q2 (R1) guidelines and the measured accuracy and precision are assessed to be within the accepted limits.

A sensitive, simple and rapid stability-indicating HPLC method using fluorescence detection was developed for the quantitative determination of the antihistaminic drug cyproheptadine hydrochloride ...

Using two green and sensitive spectrofluorimetric methods, we quantified two cephalosporins, cefepime (CFM) and cefazolin (CFZ), in raw and pharmaceutical formulations. The first method is based on the reaction between CFM and fluorescamine (borate buffer, pH 8), which yields a highly fluorescent product. After excitation at 384 nm, the fluorescent product emits light at 484 nm. At concentration ranges from 12.0 to 120.0 ng ml −1 , the relative fluorescence intensity/concentration curve was linear with a limit of quantification (LOQ) of 2.46 ng ml −1 . The second method relied on measuring the CFZ quenching action on acriflavine fluorescence through formation of an ion-associate complex using Britton–Robinson buffer at pH 8. We measured acriflavine fluorescence at 505 nm after excitation at 265 nm. The decrease in acriflavine fluorescence intensity was CFZ concentration-dependent. Using this method, we quantified CFZ in concentrations ranging from 1 to 10 µg ml −1 with a LOQ of 0.48 µg ml −1 . We studied and optimized the factors influencing reaction product formation. Moreover, we adapted our methods to the investigation of the mentioned drugs in raw and pharmaceutical formulations with greatly satisfying results. We statistically validated our methods according to International Council on Harmonisation Guidelines. The obtained results were consistent with those obtained with the official high-performance liquid chromatography methods.

Chronic pain is extremely prevalent among patients with cancer. From the clinical experience, usually, an adjuvant analgesic such as tramadol HCl (TRAM) is given concurrently with anticancer drugs for relieving pain. Recently, the world pays attention to green chemistry concept in a trial to decrease the harmful impact of chemicals on our environment. Hence, attempts were performed to find out simple eco-friendly green methods for the simultaneous determination of anticancer agents and analgesics. In this study, two facile green, sensitive spectrofluorimetric approaches were conducted for the estimation of tramadol HCl (TRAM) with axitinib (AXI) or with doxorubicin HCl (DOX). The intrinsic fluorescence of TRAM and AXI was scanned in ethanol in the first approach. The investigation revealed that TRAM could be determined at 297 nm after excitation at 272 nm, while AXI has emission maxima at 401 nm and excitation maxima at 335 nm. In the second approach, aqueous solution/acetate buffer (pH 4.5) was selected as the most convenient solvent for the simultaneous estimation of TRAM and DOX. Intense native fluorescence was recognized for DOX at 592 nm after excitation at 495 nm in addition to determination of TRAM at the previously mentioned wavelength in the first approach. The study outcomes verified that the inherent nature of the solvent has a significant influence on the sensitivity, reproducibility, and quantitation of the method. A good linear correlation was attained between the relative fluorescence and the concentration in the ranges of 0.02–0.4 μg/mL for both TRAM and AXI (the first approach), 0.02–0.24 μg/mL for TRAM and 0.1–1.2 μg/mL for DOX (the second approach). Different dosage forms of the studied drugs were simply analyzed, and good recoveries were attained within the range. Moreover, the proposed approaches were successfully extended for concurrent estimation of the studied drugs in spiked human plasma after simple protein precipitation. According to ICH guidelines, the approaches were assessed regarding linearity, accuracy, and precision. The proposed approaches greenness was confirmed via applying the National Environmental Methods Index, analytical eco-scale and Green Analytical Procedure Index.

A new, robust, and reliable sweeping-micellar electrokinetic chromatography (sweeping-MEKC) method with dynamic pH junction and retention factor gradient effect (RFGE) is developed for the simultaneous determination of four different analytes in two ternary mixtures of pharmaceutical importance. The studied analytes are drotaverine hydrochloride and caffeine combined with paracetamol (Mixture-I) or dipyrone (Mixture-II). Different experimental parameters are carefully investigated in order to achieve the highest possible resolution and sensitivity in a short analysis time. A special interest is given to the effect of sample matrix composition on the attainable enrichment efficiency with a focus on dynamic pH junction and RFGE. Up to 8 times increase in sensitivity is achieved by the modification of the sample matrix. The theoretical considerations of the underlying effects regarding the separation and the enrichment processes are thoroughly discussed. A full validation study of the developed method based on the pharmacopeial guidelines is performed. The method is successfully applied to the analysis of the studied drugs in their co-formulated or single-ingredient tablet preparations with a total run time of less than 11 min.

In this study, two analytical approaches were exploited for the resolution of binary mixtures of ciprofloxacin HCl (CIP) or norfloxacin (NOR) and phenazopyridine HCl (PHZ). In the first approach, the amplitudes of the first derivative of the ratio spectra were measured at 267 or 287 nm for CIP and at 268 or 291 nm for NOR. PHZ could be directly determined in the presence of CIP or NOR at 405 nm. The calibration graphs were rectilinear over the ranges of 1.0–16.0 µg/mL for CIP or NOR and 1.0–10.0 µg/mL for PHZ. In the second approach, an accurate, reliable and environmentally nontoxic micellar liquid chromatographic (MLC) method was developed. A good chromatographic separation was achieved using a 150 mm × 4.6 mm i.d., 5 µm particle size Spherisorb ODS-2 column. Eco-friendly mobile phase containing 0.12 M sodium dodecyl sulphate, 0.3% triethylamine and 6% n-butanol in 0.02 M orthophosphoric acid of pH 3.0 was pumped at a flow rate of 1 mL/min. Time programmed UV-detection was applied to allow sensitive determination of the studied drugs. The analytes were eluted without interferences in

In this study, a new electrogenerated chemiluminescence (ECL) reaction is presented through an oxidative-reductive pathway for amisulpride (AMS) as a new coreactant and Ru(bpy)32+ luminophore for the first time. The unique chemical structure of AMS through the presence of electroactive tertiary amino group in combination with the presence bulky electron donating group attached to α‑carbon of its amino group demonstrates the dramatic increase in ECL intensity of luminophore. Upon electrochemical oxidation of both the AMS and Ru(bpy)32+, the electrogenerated AMS+ undergoes spontaneous deprotonation to produce strong reductant that is reacted with electrogenerated Ru(bpy)33+ for excited state production. The developed method presented highly sensitive, selective, rapid, simple and cost-effective ECL approach for AMS detection. Under optimized parameters, the ECL-concentration plot showed a good linear relationship between ECL intensity and AMS concentrations in presence of 1.0 mM Ru(bpy)32+ over the concentration range of (5.0 × 10−10–2.0 × 10−7 M) with a lower detection limit of 7.6 × 10−9 M and a lower quantification limit of 2.51 × 10−8 M. The developed ECL method is successfully utilized for the determination of AMS in Amipride tablets and real human plasma.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of Amlexanox (AMX) in its bioadhesive buccal tablets. The proposed method is based on measuring the native fluorescence of the methanolic solution of AMX at 400 nm after excitation at 242 nm in 0.2 M borate buffer (pH 10) and 0.5% w/v sodium dodecyl sulfate (SDS) solution. The interaction of AMX with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of AMX. The relative fluorescence intensity-concentration plot was rectilinear over the range 5.0-80.0 ng/mL, with a lower detection limit of 0.57 ng/mL and a lower quantification limit of 1.74 ng/mL. The proposed method was successfully applied to the analysis of AMX in its commercial tablets. Moreover, content uniformity testing was conducted by applying official USP guidelines. Statistical evaluation and comparison of the data obtained using the proposed and comparison methods revealed good accuracy and precision for the proposed method.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of lacidipine (LCP) in tablets. The proposed method is based on the investigation of the fluorescence spectral behavior of LCP in both sodium dodecyl sulphate (SDS) and the tween-80 micellar system. In aqueous solutions of acetate buffer (pH 4.5), the fluorescence intensities of LCP were greatly enhanced (ca. 2.4 and 4.3 folds) in the presence of either SDS or tween-80, respectively. The fluorescence intensity was measured at 444 nm after excitation at 277 nm using either SDS or tween-80 as a surfactant. The fluorescence–concentration plots were rectilinear over the ranges of 50.0–500.0 ng/ml and 5.0–200.0 ng/ml with lower detection limits of 5.11 and 2.06 ng/ml and lower quantification limits of 17 and 6.87 ng/ml using SDS and tween-80, respectively. The method was successfully applied to the analysis of LCP in commercial tablets and the results were in good agreement with those obtained with the comparison method. Furthermore, content uniformity testing of pharmaceutical tablets was also conducted. Copyright © 2014 John Wiley & Sons, Ltd.

Two accurate analytical methods were developed for the resolution and analysis of a binary mixture of acemetacin (ACE) and chlorzoxazone (CLZ). The first method depends on chromatographic separation of ACE and CLZ using a Shimadzu VP-ODS column. Mobile phase containing 0.075 M sodium dodecyl sulphate, 0.3% triethylamine, 10% n-propanol in 0.02 M orthophosphoric acid of pH 5.5 was pumped at a flow rate of 1 mL/min. with UV detection at 210 nm. The method was further extended to the determination of acemetacin (ACE) and chlorzoxazone (CLZ) in spiked human plasma without prior extraction. For the second method, it depends on measuring the amplitudes of the first derivative spectra at 281.75 nm for ACE and 242.53 nm for CLZ.

New, selective, and accurate HPLC methods are described for the analysis of two ternary mixtures used for migraine treatment containing drotaverine hydrochloride (DRT) with caffeine (CAF), and dipyrone (DIP) (mixture I), or paracetamol (PAR) (mixture II). The described methods used a mobile phase consisting of methanol: 0.02 M sodium dihydrogen phosphate in two different ratios. The pH of the mobile phases was adjusted to 4 and UV detection at 220 nm was used. Good chromatographic separations were achieved using Promosil C18 column. Spironolactone (SPL) and propranolol (PRP) were used as internal standards (ISs) for mix. I and II, respectively.

A simple, sensitive and rapid spectrofluorimetric method was developed for the determination of esomeprazole (EMZ) and pantoprazole (PRZ) in their pharmaceutical formulations and human plasma. The proposed method is based on the fluorescence spectral behavior of EMZ in methanol in the presence of 0.1 m NaOH containing 0.5% methyl cellulose (MC) at 306/345 nm. The fluorescence intensity of EMZ was enhanced about 1.3-fold and good linearity in the range 0.4-4.0 µg/mL with a lower detection limit of 0.04 µg/mL and lower quantification limit of 0.14 µg/mL. For PRZ, its methanolic solution exhibited marked native fluorescence at 290/325 nm after enhancement (about 2.1- or 1.4-fold) using either 0.025% sodium dodecyl sulfate (SDS) or 0.05% MC in the presence of 0.2 m borate buffer of pH 9.5. The fluorescence-concentration plots of PRZ were rectilinear over the ranges 0.2-2.0 and 0.3-3.0 µg/mL with lower detection limits of 0.02 and 0.03 µg/mL and lower quantification limits of 0.07 and 0.09 µg/mL using sodium dodecyl sulfate and MC, respectively. The method was successfully applied to the analysis of EMZ and PRZ in their commercial dosage forms and the results were in good agreement with those obtained with the comparison method. Furthermore, in a preliminary investigation, the proposed method was extended to the in vitro determination of the two drugs in spiked human plasma and the results were satisfactory.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of amisulpride (AMS) and bumidazone (BUM) in tablet form. The proposed method is based on measuring the native fluorescence of the studied drugs in methanol at 360 and 344 nm after excitation at 276 and 232 nm for AMS and BUM, respectively. The fluorescence–concentration plots were rectilinear over the ranges of 5.0–60.0 ng/mL for AMS and 0.5–5.0 µg/mL for BUM. The lower detection limits were 0.70 ng/mL and 0.06 µg/mL, and the lower quantification limits were 2.0 ng/mL and 0.18 µg/mL for AMS and BUM, respectively. The method was successfully applied for the analysis of AMS and BUM in commercial tablets. Statistical evaluation and comparison of the data obtained using the proposed and comparison methods revealed good accuracy and precision for the proposed method. Copyright © 2014 John Wiley & Sons, Ltd.

Two simple analytical methods were developed and validated for the analysis of a binary mixture of metoclopramide (MET) and aspirin (ASP). The first method depends on measuring the first derivative amplitudes at 257 nm for MET and at 310 nm for ASP, respectively. The calibration graphs were linear in the range of 0.25-20.0 µg/mL for MET and 10.0-200.0 µg/mL for ASP. For the second method, good chromatographic separation was achieved using Promosil C18 column (250 × 4.6 mm i.d., 5 µm particle size). Mobile phase consisting of methanol and 0.02 M phosphate buffer in the ratio of 60:40 (v/v) at pH 4.0 was pumped at a flow rate of 1 mL/min with UV detection at 260 nm. Indapamide was used as an internal standard. The method showed good linearity over the concentration ranges of 0.20-10.0 and 10.0-200.0 μg/mL with limits of detection of 0.06, 1.81 μg/mL and limits of quantification of 0.17, 5.46 μg/mL for MET and ASP, respectively. The results of the proposed methods were statistically compared with those obtained by the official United States Pharmacopeia method revealing non-significant differences in the performance of the methods regarding accuracy and precision. The suggested methods were successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets as well as in their single dosage forms.

A simple and sensitive high-performance liquid chromatography method was developed and validated for the determination of calcium dobesilate (DOB) or ethamsylate (ETM) in the presence of their degradation product, hydroquinone (HQ). The analyses were carried out on Promosil C18 column (4.6 mm × 250 mm, 5 µm particle size) using an ion-pair mobile phase consisting of methanol–1.5 mm tetra-butyl ammonium bromide in 0.06 m phosphate buffer (25 : 75, v/v) at pH 6.0 with fluorescence detection at 286/333 nm. Pindolol was used as an internal standard. The proposed method was found to be rectilinear over the concentration ranges of 0.05–0.5 µg/mL for DOB, 0.1–0.8 µg/mL for ETM and 0.005–0.1 µg/mL for HQ. The method was applied for the determination of the studied drugs in different dosage forms and biological fluids. The results of the proposed method were statistically compared with those obtained by the comparison methods revealing no significance differences in the performance of the methods regarding accuracy and precision. Moreover, applying a time-programmed fluorescence technique was valuable for the detection of trace amounts of HQ as an impurity and allowed purity testing of ETM or DOB within the BP pharmacopeial limit (0.1%). Copyright © 2013 John Wiley & Sons, Ltd.

Background Adapalene is a retinoid analogue with actions similar to those of tretinoin. It is used in topical treatment of mild to moderate acne. A survey of the literature reveals that no spectrofluorimetric method has been reported yet for determination of ADP, so it was thought necessary to develop a highly sensitive stability indicating spectrofluorimetric method. Results Two highly sensitive spectrofluorimetric approaches were conducted for the assay of adapalene (ADP) in its gel. In the first approach, ADP exhibits an intense native fluorescence at 389 nm after excitation at 312 nm using borate buffer (pH 7.0)/ethanol system. This approach was successfully applied for routine analysis of ADP in its gel and ideally suited to the in vitro diffusion test. To elucidate the inherent stability of ADP, bulk sample was subjected to different stress conditions as specified by ICH guidelines. The acidic and oxidative degradation products were resolved from the intact drug using second and first derivative synchronous fluorimetry at 346 and 312.45 nm, respectively (the second approach). The synchronous fluorescence was scanned at Δ λ of 80 nm in case of acidic degradation and at Δ λ of 100 nm in case of oxidative degradation. Good linearity was obtained for ADP over the range 2.0–14.0 ng/mL with good correlation coefficient 0.999 in each approach. The approaches were carefully examined in terms of linearity, accuracy and precision. They were suitable for routine quality control laboratory. Moreover, the stability-indicating power of the second approach was ascertained via forced degradation studies. Conclusions The proposed approaches were validated and successfully applied for the quantitative assay of a small concentration of ADP in its pharmaceutical gel. The conventional spectrofluorimetry was ideally suited for in vitro diffusion test. Stability studies were also conducted using different forced degradation condition according to ICH recommendation.Graphical abstractSimultaneous determination of ADP and its degradation products.

Two simple and accurate analytical methods were developed for the resolution and analysis of a binary mixture of hydrochlorothiazide (HCT) and pindolol (PIN), based on using a ratio derivative spectrophotometric technique and a micellar liquid chromatographic method. The first method depends on measuring the amplitudes of the first derivative of the ratio spectra at 337.2 nm for HCT and 294.4 nm for PIN. The calibration graphs were linear over the range of 5–40 µg/mL for HCT and 2–32 µg/mL for PIN. For the second method, good chromatographic separation was achieved using a 250 mm × 4.6 mm i.d., 5 µm particle size Symmetry C18 column. Mobile phase containing 0.15 M sodium dodecyl sulfate, 0.3% triethylamine, and 18% methanol in 0.02 M orthophosphoric acid of pH 3.0 was pumped at a flow rate of 1 mL/min with UV detection at 254 nm. Indapamide (IND) was used as an internal standard (IS). The method showed good linearity over the concentration ranges of 2–30 µg/mL and 2–40 µg/mL with limits of detection of 0....

The study represents the first report on the development of spectrophotometric methods for determination of ethamsylate (EST) in the presence of hydroquinone as an impurity and/or acidic degradation product. The proposed methods are based on the reaction of EST through it,s secondary amino group either with 1,2-naphthoquinone-4-sulphonate sodium (NQS) at pH 10.7 or 2,4-dinitrofluorobenzene (DNFB) at pH 9.3 to form orange and yellow colored reaction products peaking at 478 and 387 nm for methods (I) and (II), respectively. The different experimental parameters affecting the development and stability of the reaction products in methods (I) and (II) were carefully studied and optimized. The absorbance-concentration plots were rectilinear over the concentration ranges of 2-30 and 2-14 µg mL−1 for methods (I) and (II), respectively. The lower detection limits were 0.13 and 0.19 µg mL−1 and the lower quantitation limits were 0.44 and 0.63 µg mL−1 for methods (I) and (II), respectively. Both methods were successfully applied to commercial ampoules and tablets.

Two simple, sensitive and accurate spectrophotometric methods have been developed for the determination of bumadizone in bulk drug and its tablets. Both methods based on the oxidative coupling reaction with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) and measuring the absorbance of the developed colors by direct or kinetic spectrophotometric method. Upon treatment of a mixture of the chromogenic reagent and drug with cerium (IV) ammonium sulfate (method I) or ferric chloride (method I), a red or violet color was developed immediately or after 30 minutes measurable at 557 nm for method I or II, respectively. The absorbance-concentration plots were rectilinear over the ranges of 1-10 μg/mL (r = 0.9999) for method I and 2-16 μg/mL (r = 0.9998) for method II. The detection limits were 0.15 and 0.27 μg/mL & the quantitation limits were 0.46 and 0.84 μg/mL for methods I and II, respectively. Different experimental parameters affecting the development and stability of the reactions products were studied and optimized. The proposed methods were applied successfully to the determination of bumadizone in its tablets, and the results obtained were in good agreement with those obtained using a comparison method.

A highly simple and sensitive kinetic spectrofluorometric method was developed for the determination of thioctic acid. The method is based on the oxidation of the studied drug with cerium(IV) ammonium sulfate in acidic medium. The fluorescence of the produced Ce(III) was measured at 365 nm after excitation at 255 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The method is applicable over the concentration range of 0. 02 to 0.12 μg/mL with a detection limit of 6.06 x 10 -3 μg/mL and a quantification limit of 0.02 μg/mL. The method was successfully applied for the assay of the studied drug in pharmaceutical formulations. The results obtained were in good agreement with those obtained with the reference method.

Three simple and sensitive spectrophotometric methods were developed for the determination of thioctic acid in bulk and in its pharmaceutical preparations using iron(III) as an oxidizing agent. Method A is based on kinetic investigation of oxidation reaction of the drug with iron(III) and a subsequent chelation of the produced iron(II) with ferricyanide to form prussian blue colored product at room temperature for a fixed time of 15 minutes at 750 nm. Methods B and C are based on oxidation of the studied drug with iron(III). The equivalent iron(II) produced is allowed to react with either o-phenanthroline or bipyridyl to give colored species measurable at 510, 522 nm, respectively. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration ranges of 0.4–4 μg/mL with a detection limit of 0.095 μg/mL for method A and 0.5–5 μg/mL with detection limits 0.137 and 0.127 for method B and C, respectively. The three methods were successfully applied for the determination of the drug in its dosage forms. The percentage recoveries were 99.88 ± 1.40, 99.98 ± 1.26 and 100.64 ± 1.07, respectively.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of Amlexanox (AMX) in its bioadhesive buccal tablets. The proposed method is based on measuring the native fluorescence of the methanolic solution of AMX at 400 nm after excitation at 242 nm in 0.2 M borate buffer (pH 10) and 0.5% w/v sodium dodecyl sulfate (SDS) solution. The interaction of AMX with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of AMX. The relative fluorescence intensity-concentration plot was rectilinear over the range 5.0-80.0 ng/mL, with a lower detection limit of 0.57 ng/mL and a lower quantification limit of 1.74 ng/mL. The proposed method was successfully applied to the analysis of AMX in its commercial tablets. Moreover, content uniformity testing was conducted by applying official USP guidelines. Statistical evaluation and comparison of the data obtained using the proposed and comparison methods revealed good accuracy and precision for the proposed method.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of amisulpride (AMS) and bumidazone (BUM) in tablet form. The proposed method is based on measuring the native fluorescence of the studied drugs in methanol at 360 and 344 nm after excitation at 276 and 232 nm for AMS and BUM, respectively. The fluorescence-concentration plots were rectilinear over the ranges of 5.0-60.0 ng/mL for AMS and 0.5-5.0 µg/mL for BUM. The lower detection limits were 0.70 ng/mL and 0.06 µg/mL, and the lower quantification limits were 2.0 ng/mL and 0.18 µg/mL for AMS and BUM, respectively. The method was successfully applied for the analysis of AMS and BUM in commercial tablets. Statistical evaluation and comparison of the data obtained using the proposed and comparison methods revealed good accuracy and precision for the proposed method.

A simple and sensitive high-performance liquid chromatography method was developed and validated for the determination of calcium dobesilate (DOB) or ethamsylate (ETM) in the presence of their degradation product, hydroquinone (HQ). The analyses were carried out on Promosil C18 column (4.6 mM × 250 mM, 5 µm particle size) using an ion-pair mobile phase consisting of methanol-1.5 mM tetra-butyl ammonium bromide in 0.06 M phosphate buffer (25 : 75, v/v) at pH 6.0 with fluorescence detection at 286/333 nm. Pindolol was used as an internal standard. The proposed method was found to be rectilinear over the concentration ranges of 0.05-0.5 µg/mL for DOB, 0.1-0.8 µg/mL for ETM and 0.005-0.1 µg/mL for HQ. The method was applied for the determination of the studied drugs in different dosage forms and biological fluids. The results of the proposed method were statistically compared with those obtained by the comparison methods revealing no significance differences in the performance of the methods regarding accuracy and precision. Moreover, applying a time-programmed fluorescence technique was valuable for the detection of trace amounts of HQ as an impurity and allowed purity testing of ETM or DOB within the BP pharmacopeial limit (0.1%).

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.

A highly sensitive and simple spectrofluorimetric method has been developed for the determination of almotriptan malate (ALM) and zolmitriptan (ZOL) in their pharmaceutical preparations. The proposed method is based on the investigation of the fluorescence spectral behavior of the two drugs in aqueous acidic systems. The fluorescence intensity was measured at 360 and 350 nm after excitation at 270 nm for ALM and ZOL, respectively. The fluorescence–concentration plots were rectilinear over the range 0.1–1.2 μg mL−1 and 5–40 ng mL−1, with lower detection limits of 0.03 μg mL−1 and 0.70 ng mL−1 for ALM and ZOL, respectively. The proposed method was successfully applied for the assay of commercial tablets as well as for content uniformity testing. The application of the proposed method was extended to the assay of ZOL in biological fluids. The results were statistically compared to those obtained by comparison methods and were found to be in good agreement.

A new, specific, and sensitive RP-HPLC method was developed for the simultaneous determination of eprosartan (EPR) and hydrochlorothiazide (HCT). Good chromatographic separation was achieved using a 250 × 4.6 mm id, 5 μm particle size Symmetry® C18 column. The mobile phase acetonitrile–0.1 M phosphate buffer (35 + 65, v/v), pH 4.5, was pumped at a flow rate of 1 mL/min, with UV detection at 275 nm. The method showed good linearity in the ranges of 0.5–50 and 0.1–10 μg/mL, with LOD of 0.06 and 0.02 μg/mL and LOQ of 0.20 and 0.08 μg/mL for EPR and HCT, respectively. The proposed method was successfully applied for the analysis of the studied drugs in their synthetic mixture and co-formulated tablets. The method was further extended to the in vitro and in vivo determination of the two drugs in spiked and real human plasma. Interference likely to be encountered from the co-administered drugs was studied.