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Guaifenesin (GUA) is determined in dosage forms and plasma using two methods. The spectrofluorimetric technique relies on the measurement of native fluorescence intensity at 302 nm upon excitation wavelength "223 nm". The method was validated according to ICH and FDA guidelines. A concentration range of 0.1-1.1 μg/mL was used, with limit of detection (LOD) and quantification (LOQ) values 0.03 and 0.08 µg/mL, respectively. This method was used to measure GUA in tablets and plasma, with %recovery of 100.44% ± 0.037 and 101.03% ± 0.751. Furthermore, multivariate chemometric-assisted spectrophotometric methods are used for the determination of GUA, paracetamol (PARA), oxomemazine (OXO), and sodium benzoate (SB) in their lab mixtures. The concentration ranges of 2.0-10.0, 4.0-16.0, 2.0-10.0, and 3.0-10.0 µg/mL for OXO, GUA, PARA, and SB; respectively, were used. LOD and LOQ were 0.33, 0.68, 0.28, and 0.29 µg/mL, and 1.00, 2.06, 0.84, and 0.87 µg/mL for PARA, GUA, OXO, and SB. For the suppository application, the partial least square (PLS) model was used with %recovery 98.49% ± 0.5, 98.51% ± 0.64, 100.21% ± 0.36 & 98.13% ± 0.51, although the multivariate curve resolution alternating least-squares (MCR-ALS) model was used with %recovery 101.39 ± 0.45, 99.19 ± 0.2, 100.24 ± 0.12, and 98.61 ± 0.32 for OXO, GUA, PARA, and SB. Analytical Eco-scale and Analytical Greenness Assessment were used to assess the greenness level of our techniques., (© 2024. The Author(s).)

Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for simultaneous determination of montelukast sodium (MKT) and loratadine (LRT). The first method was based on chromatographic separation performed on precoated silica gel 60 GF254 plates with ethyl acetate-ethanol 9: 1 (v/v) as the mobile phase. The developed plates were scanned and quantified at 260 nm. The method gives linear correlation over concentration ranges of 0.3-3.6 μg/spot and 0.2-4.0 μg/spot for MKT and LRT, respectively. It was also successfully applied to analysis of both drugs in their pharmaceutical preparation and human plasma. The other methods are UV-spectrophotometric methods based on smart spectra manipulating to zero order spectrum of each drug. These methods are named response correlation (RC), a-centering and ratio derivative methods. RC and a-centering methods were dependent on the presence of an isosbestic point between the overlapped spectra of both drugs. While ratio derivative method based on manipulation of the ratio spectra of both drugs. The two drugs obey Beer-Lambert law over the concentration ranges of 3.0-30.0 μg/mL in the three spectrophotometric methods. Moreover, the greenness of the developed methods is assessed using suitable analytical Eco-Scale and Green Analytical Procedure Index., (Published by Oxford University Press 2023.)

Nowadays, a huge population consumes Dietary supplements for losing weight. Products are often claimed as botanical blends, yet they aren't necessarily safe. Misleading labels are also very common. Thus, validated analytical methods for a wide range of slimming compounds are highly needed. Herein, we present a simple HPLC/PDA method for the quantitation of seven popular slimming ingredients. Studied compounds were Caffeine, Raspberry Ketone, trans-Resveratrol, p-Synephrine, p-Octopamine, p-Hordenine and 2-phenethylamine. After optimization, separation was carried out on a C18 column and mobile phase was a mixture of Acetonitrile:Water containing 0.1% phosphoric acid (50:50, %v/v). The last compound was eluted at 9.76 min. Separation was efficient showing baseline- separated symmetric peaks, without using any gradient programs, organic mobile phase modifiers or modified stationary phases. Method validation was done following ICH guidelines. Calibration curves were linear over wide concentration ranges and calculated LOD values were in the range 0.02-0.09 µg/mL. Method greenness was assessed using Analytical Eco-scale, GAPI and AGREE metric tools. Further, four random sample products purchased from online supplement stores were assayed. Results proved some mislabeling actions. To support our findings, standard addition was carried out and average % recoveries were 96.67 - 101.44% with standard deviation ≤ 2.83 between measurements., (© 2022. The Author(s).)

Combining short-acting and long-acting insulin analogs was a real challenge that was overcome by NovoNordisk through the co-formulation of insulin aspart and insulin degludec in single-dosage form. The proposed study provides a simple, short, and reliable HPLC method with diode array detection that is developed and validated for the simultaneous determination of insulin aspart and insulin degludec in human plasma. The proposed method achieved good separation between the two analytes utilizing a C8 column at 35°C in a very short run time (6 min), with a simple, low-cost, and reliable extraction method through precipitation of plasma protein. Gradient elution was applied using a mobile phase consisting of 0.1 M sodium sulfate (pH 3.4) and acetonitrile. The method was validated according to EMA Guideline on Bioanalytical Validation. The proposed method had a linear range from 3.0 to 300 μg/mL for insulin aspart and from 3.5 to 300 μg/mL for insulin degludec. The intra- and inter-day precision of insulin aspart were 0.36-3.33% and 1.59-8.84%, respectively, and accuracy was between 10.06 and 3.09% The intra- and inter-day precision of insulin degludec were 0.29-1.93% and 0.89-5.14%, respectively, and accuracy was between -5.29 and 3.91%., (© 2021 John Wiley & Sons, Ltd.)

Although Dietary supplements are readily accessible and extensively used worldwide, they are inadequately regulated and consumers are victims of manufacturers' fraud. Thus, quality regulations are required to ensure safety of products available to the public. We propose the first native spectrofluorimetric quality control assay of raspberry ketone, a popular dietary supplement ingredient for weight loss. This work relies on the constant wavelength synchronous scan of the Raspberry Ketone native fluorescence, overcoming the demerits of conventional excitation/ emission spectra. For the best measurement conditions, several parameters were optimized including Δλ value, diluting solvent, medium pH and the effect of surfactants/ macromolecules. In aqueous medium (Δλ = 110 nm), a linear relationship exists between synchronous fluorescence intensity at peak maximum 405.6 nm and solution concentration in the range 300-1500 ng/mL. Method sensitivity was recorded with LOD and LOQ values 60.63 and 183.72 ng/mL; respectively. Validation was done in accordance to International Conference on Harmonization (ICH) guidelines. This simple procedure was successfully applied to the analysis of Raspberry Ketone in commercially available dietary supplement capsules with average recovery 98.67% ± 1.74 and further extended to weight variation testing following the official United States Pharmacopeial (USP) guidelines. Finally, green assessment was done using the ''Analytical Eco-scale'' tool. The total score was 89/100 points revealing excellent greenness of our proposal. Our proposal is simple, eco-friendly and cheap. It can be conveniently adopted for routine quality control practices especially in developing countries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Recently, functional polymers have attracted significant attention in the areas of pharmaceuticals and biomedical applications, so it is important to develop simple techniques to analyze functional polymers in their pharmaceutical dosage forms., Objective: Three simple, accurate, and sensitive UV spectrophotometric methods have been developed and validated for determination of polyvinyl pyrrolidone (PVP) in the presence of benzalkonium chloride (BZ) and sodium lactate in ternary mixtures., Method: Method A is a derivative ratio spectra zero-crossing (DRSZ) method which measures PVP peak amplitude at 303.1 nm. Method B is a double divisor ratio derivative (DDRD), used for determination of both PVP and BZ in the presence of sodium lactate at 272.6 and 271.5 nm, respectively. Method C is a double divisor ratio derivative-ratio difference spectrophotometric method (DDRD-RDSM), a new and hybrid method of double divisor and ratio difference that hasn't been applied before. It measures peak amplitude difference of the ratio spectra at ΔP278 - 252.4 and ΔP260.9 - 213 for PVP and BZ, respectively., Results: Linear ranges for PVP (5.00-35.00, 10.00-40.00, and 10.00-40.00 µg/mL) was obtained by using DRSZ, DDRD, and DDRD-RDSM, respectively. While the linear range for BZ (5.00-60 µg/mL) was obtained by using both DDRD and DDRD-RDSM., Conclusions: All results were statistically compared with reported methods. No significant differences were observed. The developed methods were applied to the analysis of the investigated drugs in pure and pharmaceutical dosage forms., Highlights: The proposed methods are of great value, improving the efficiency of routine analysis of PVP and BZ in their pharmaceutical dosage forms., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Stress testing of biopharmaceuticals plays an important role in preparation of their stability profiles through investigation of possible degradation pathways and identification of degradation products, so in this study Insulin Degludec which is a new generation ultra-long-acting basal insulin is subjected to stress conditions as different temperatures, different pH, oxidation, mechanical agitation, and repeated freeze and thaw cycles to generate possible degradation products and aggregation that are investigated by two new validated RP-HPLC and SEC-HPLC methods in addition to dynamic light scattering (DLS) and native polyacrylamide gel electrophoresis (Nu-PAGE). SEC-HPLC was used to investigate formation of aggregates whose results were correlated with those obtained from DLS and Nu-PAGE, while RP-HPLC was used to investigate any possible chemical modifications. The Proposed RP-method had limit of detection (LOD) and limit of quantitation (LOQ) of 0.012 mg/mL and 0.045 mg/mL respectively and accuracy of 99.22 ± 1.07 %, while the SEC methods had limit of detection (LOD) and limit of quantitation (LOQ) of 0.012 mg/mL and 0.031 mg/mL, respectively. The degradation pattern due to high temperature effect and oxidation is investigated by LC- tandem mass spectrometry. Results showed that Insulin degludec is highly stable under low temperature, mechanical agitation and repeated freeze and thaw stress conditions but elevated temperature and high acidic condition lead to formation of aggregates and also chemical modifications including deamidation, isomerization and oxidation. Such different chemical degradation pathways are due to presence of variable reactive moieties in Insulin degludec structure. Insulin degludec is highly vulnerable to oxidation at the sulfur containing cysteine residue in B chain in position B7 forming trioxidation derivative when exposed to hydrogen peroxide. Formation of A21-Asp and A18-Asp deamidated variants as well as B3-Asp and B3-isoAsp deamidated variants are prominent degradation pathways at neutral pH but at elevated temperature., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A simple, precise, rapid and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for analysis of safinamide mesylate (SAF) in presence of its basic degradate, and co-administered drugs levodopa and ondansetron. The mobile phase consisted of acetonitrile and 20 mM potassium dihyrogen orthophosphate buffer having pH = 5 (40: 60 v/v). Quantification was achieved with ultraviolet detector at 226 nm. The linear range was 0.5-10 μg/mL with mean recovery ± SD of 99.72 ± 1.59. The peak purity of SAF in pharmaceutical preparation spiked with its degradate and co-administered drugs revealed symmetry factor (999.8) within the calculated threshold (>998.1). The suggested method was validated in compliance with the International Conference on Harmonization (ICH) guidelines and statistically compared with the manufacturer HPLC method with no significant difference in terms of accuracy and precision. The assay method was successfully used to estimate SAF in tablets with good percentage recoveries. The high sensitivity (lower than Cmax of the drug 0.65 μg/mL) of the proposed HPLC method enabled the determination of SAF in presence of its basic degradate and co-administered drug, ondansetron in human plasma with acceptable accuracy. The suggested HPLC method could be used in Quality Control (QC) lab for analysis of the studied drug in pharmaceutical preparation., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Egypt has the highest prevalence of hepatitis C virus (HCV) in the world thus it launched a national program for eliminating HCV aiming to treat 300,000 HCV patients per year. Three anti-HCV co-administered drugs; ribavirin (RBV), sofosbuvir (SF) daclatasvir (DAC) were simultaneously determined in human plasma by a validated, simple and sensitive RP-HPLC method using propyl paraben as an internal standard. Liquid-liquid extraction using ethyl acetate was used for samples extraction. Chromatographic separation was achieved on Scharlau® C18 column (250 × 4.6 mm2, 5 μm). Gradient elution was employed with a mobile phase mixture of water and acetonitrile at a flow rate 1 mL/min. UV detection using photodiode array detector was carried out at 207, 260 and 312 nm for RBV, SF and DAC, respectively. Method validation was performed according to the FDA guidelines for bioanalytical method validation. The calibration curves were linear over the ranges (0.5-80, 0.1-40 and 0.5-80 μg/mL) with average recoveries (100.64-108.28%, 98.48-105.91% and 97.68-101.38%) for RBV, SF and DAC, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Stability assays revealed that the three studied analytes were stable during sample storage, preparation and injection. The method can be successfully applied in routine analysis of plasma of HCV patients treated with this combination therapy which aids in therapeutic drug monitoring and patients' follow-up especially in Egypt and other developing countries fighting HCV., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Several emerging nano scale forms of carbon are showing great promise in electrochemical sensing such as graphene and multi-walled carbon nanotubes (MWCNTs). Herein we present an ecofriendly method to fabricate long life and sensitive ion selective sensors based on graphene and MWCNTs nanocomposites with no need for volatile organic solvents. Both sensors were fabricated, for the analysis of carbachol in ophthalmic solutions, plasma and urine where ion- association complex was formed between cationic carbachol and anionic Sodium tetra phenyl borate (NaTBP) in a ratio 1:1. Both sensors were evaluated according to the IUPAC recommendation data, revealing linear response in the concentration range 10 -7 M to 10 -2 M with near Nernstian slopes 50.80 ± 5 and 58.14 ± 3 mV/decade and correlation coefficients 0.9992 and 0.9998 for graphene and MWCNTs based sensors, respectively. Both sensors were successfully applied as stability indicating method for the analysis of carbachol in presence of its metabolite choline, in ophthalmic preparations, in plasma and urine showing good recovery percentage values. MWCNTs based sensor showed some advantages over graphene sensor regarding lower limit of detection (LOD), longer life time and higher selectivity towards carbachol. Statistical comparison of the proposed sensors with the official method showed no significant difference for accuracy and precision.

Graphene is the ''new star'' material for electrochemical sensing. It has unique mechanical, thermal and electrical properties, in addition to its ultra light weight. In the present work we combine for the first time the special features offered by graphene and the advantages of ion selective potentiometric sensors in a single study. We propose two types of sensors, a graphene based carbon paste and a poly vinyl chloride (PVC) based membrane sensors for the analysis of Vilazodone hydrochloride in bulk, human plasma and formula milk samples. Electro active agent is an ion- association complex based on coupling of Vilazodone cationic cite with anionic cite of Molybdate ion in a ratio 1:1. Both sensors are evaluated according to the IUPAC recommendation data, revealing linear response in the concentration range 10 -7 - 10 -3 and10 -8 - 10 -3 M with a Nernestian slope 59.89 and 59.91 mV/decade for PVC membrane and Carbon paste sensors, respectively. Both sensors were successfully applied to the analysis of Vilazodone HCl in human plasma and formula milk samples showing good recovery percentage values. Graphene based carbon paste sensor shows several advantages over conventional PVC membrane sensor regarding lower limit of detection, faster response time, longer life time and higher selectivity towards target ion., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Gradient reversed-phase high-performance liquid chromatography with photodiode array detection was used for separation, detection and quantification of bisphenol-A-diglycidyl ether (BADGE) and some of its reaction products, namely, BADGE·HCl·H2O, BADGE·H2O and BADGE·2HCl in pure form and in canned foods, where canned beans and tuna were used as representatives of aqueous and oil-in-water food matrices, respectively. The proposed method had a linear range of 0.01-0.5 μg g-1 for BADGE·HCl·H2O, BADGE·H2O, BADGE·2HCl and 0.02-0.7 μg g-1 for BADGE in aqueous food matrices. In oil-in-water matrices, the method was proven to be sensitive over a linear range of 0.01-0.5 μg g-1 for BADGE·HCl·H2O, BADGE·H2O and 0.02-0.7 μg g-1 for BADGE·2HCl and BADGE. The limits of detection and quantification ranged from 0.24 to 1.22 ng g-1 and 0.73 to 14.07 ng g-1, respectively. Excellent intraday and interday precision (n = 9) were obtained with RSD% of 0.84-2.19% and 1.88-2.52%, respectively. Accuracy was measured at five concentration levels and the recoveries ranged from 96.31% to 98.76% with an acceptable variation of ±0.9-2.87. Results suggest that the proposed method could be applied for the routine analysis of the studied compounds in their laboratory-prepared mixtures and in various types of canned foods following the limits and regulations of the European Union.

Two multivariate calibration methods, namely principal component regression (PCR) and partial least squares (PLS-2) have been developed, validated and compared for the simultaneous determination of bisphenol-A-diglycidyl ether (BADGE) and some of its reaction products, including BADGE·HCl·H 2 O, BADGE·H 2 O and BADGE·2HCl. Chemometrics allowed rapid, accurate and precise simultaneous quantification of the analytes of interest which was not possible by other spectrophotometric methods due to their severe spectral overlap. PCR and PLS-2 techniques successfully quantified BADGE, BADGE·HCl·H 2 O, BADGE·H 2 O and BADGE·2HCl in the ranges of 1.4-3.4, 1-5, 1-4.2 and 1-7 μg mL -1 , respectively. The constructed models were validated according to the International Conference on Harmonization guidelines and successfully applied for the determination of these compounds in pure form, laboratory prepared mixtures and in various types of canned foods following the limits and regulations of the European Union (EU) where satisfactory recovery results were obtained., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Innovative host-tailored polymers were prepared, characterized and used as recognition elements in potentiometric transducers for the selective quantification of 2,4-dichlorophenol (DCP).The polymer beads were synthesized using DCP as a template molecule, acrylamide (AM),methacrylic acid (MAA) and ethyl methacrylate (EMA) as functional monomers and divinylbenzene (DVB) and ethylene glycol dimethacrylate (EGDMA) as cross-linkers. The sensors were fabricated by the inclusion of MIPs in plasticized polyvinyl chloride (PVC) matrix. Response characteristics of the proposed sensors revealed anionic slopes of -59.2, -49.7 and -80.6 mV/decade with detection limits of 5.6 × 10 -5 ,5.9 × 10 -5 and 13.2 × 10 -5  mol/L for MIP/AM/DVB, MIP/MAA/DVB and MIP/EMA/EGDMA membrane based sensors, respectively. Good selectivity was observed over common inorganic/organic anions. Validation of the assay method according to IUPAC recommendations was justified ensuring the synthesis of good reliable novel sensors for DCP determination. The method was successfully applied for routine analysis of food taint in fish and fish farms water samples., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Synthetic antisense phosphorothioate oligonucleotides (PS) have undergone rapid development as novel therapeutic agents. The increasing significance of this class of drugs requires significant investment in the development of quality control methods. The determination of the many degradation pathways of such complex molecules presents a significant challenge. However, an understanding of the potential impurities that may arise is necessary to continue to advance these powerful new therapeutics. In this study, four different antisense oligonucleotides representing several generations of oligonucleotide therapeutic agents were evaluated under various stress conditions (pH, thermal, and oxidative stress) using ion-pairing reversed-phase liquid chromatography tandem mass spectrometry (IP-RPLC-MS/MS) to provide in-depth characterization and identification of the degradation products. The oligonucleotide samples were stressed under different pH values at 45 and 90 °C. The main degradation products were observed to be losses of nucleotide moieties from the 3'- and 5'-terminus, depurination, formation of terminal phosphorothioates, and production of ribose, ribophosphorothioates (Rp), and phosphoribophosphorothioates (pRp). Moreover, the effects of different concentrations of hydrogen peroxide were studied resulting in primarily extensive desulfurization and subsequent oxidation of the phosphorothioate linkage to produce the corresponding phosphodiester. The reaction kinetics for the degradation of the oligonucleotides under the different stress conditions were studied and were found to follow pseudo-first-order kinetics. Differences in rates exist even for oligonucleotides of similar length but consisting of different sequences. Graphical abstract Identification of degradation products across several generations of oligonucleotide therapeutics using LC-MS.

Phosphorothioate (PS) oligonucleotides are a rapidly rising class of drugs with significant therapeutic applications. However, owing to their complex structure and multistep synthesis and purification processes, generation of low-level impurities and degradation products are common. Therefore, they require significant investment in quality control and impurity identification. This requires the development of advanced methods for analysis, characterization and quantitation. In addition, the presence of the PS linkage leads to the formation of chiral centers which can affect their biological properties and therapeutic efficiency. In this review, the different types of oligonucleotide impurities and degradation products, with an emphasis on their origin, mechanism of formation and methods to reduce, prevent or even eliminate their production, will be extensively discussed. This review will focus mainly on the application of chromatographic techniques to determine these impurities but will also discuss other approaches such as mass spectrometry, capillary electrophoresis and nuclear magnetic resonance spectroscopy. Finally, the chirality and formation of diastereomer mixtures of PS oligonucleotides will be covered as well as approaches used for their characterization and the application for the development of stereochemically-controlled PS oligonucleotides., (Copyright © 2017 John Wiley & Sons, Ltd.)

Six simple, accurate, reproducible, and selective derivative spectrophotometric and chemometric methods have been developed and validated for the determination of levamisole HCl (Lev) either alone or in combination with closantel sodium (Clo) in the pharmaceutical dosage form. Lev was determined by first-derivative, first-derivative ratio, and mean-centering methods by measuring the peak amplitude at 220.8, 243.8, and 210.4 nm, respectively. The methods were linear over the concentration range 2.0-10.0 μg/mL Lev. The methods exhibited a high accuracy, with recovery data within ±1.9% and RSD <1.3% (n = 9) for the determination of Lev in the presence of Clo. Fortunately, Lev showed no significant UV absorbance at 370.6 nm, which allowed the determination of Clo over the concentration range 16.0-80.0 μg/mL using zero-order spectra, with a high precision (RSD <1.5%, n = 9). Furthermore, principal component regression and partial least-squares with optimized parameters were used for the determination of Lev in the presence of Clo. The recovery was within ±1%, with RSD <1.0% (n = 9) and root mean square error of prediction ≤1.0. The proposed methods were validated according to the International Conference on Harmonization guidelines. The proposed methods were used in the determination of Lev and Clo in a binary mixture and a pharmaceutical formulation, with high accuracy and precision.

New accurate, sensitive and selective spectrophotometric and chemometric methods were developed and subsequently validated for determination of Imipenem (IMP), ciprofloxacin hydrochloride (CIPRO), dexamethasone sodium phosphate (DEX), paracetamol (PAR) and cilastatin sodium (CIL) in human urine. These methods include a new derivative ratio method, namely extended derivative ratio (EDR), principal component regression (PCR) and partial least-squares (PLS) methods. A novel EDR method was developed for the determination of these drugs, where each component in the mixture was determined by using a mixture of the other four components as divisor. Peak amplitudes were recorded at 293.0 nm, 284.0 nm, 276.0 nm, 257.0 nm and 221.0 nm within linear concentration ranges 3.00-45.00, 1.00-15.00, 4.00-40.00, 1.50-25.00 and 4.00-50.00 μg mL(-1) for IMP, CIPRO, DEX, PAR and CIL, respectively. PCR and PLS-2 models were established for simultaneous determination of the studied drugs in the range of 3.00-15.00, 1.00-13.00, 4.00-12.00, 1.50-9.50, and 4.00-12.00 μg mL(-1) for IMP, CIPRO, DEX, PAR and CIL, respectively, by using eighteen mixtures as calibration set and seven mixtures as validation set. The suggested methods were validated according to the International Conference of Harmonization (ICH) guidelines and the results revealed that they were accurate, precise and reproducible. The obtained results were statistically compared with those of the published methods and there was no significant difference., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Two stability indicating spectrofluorimetric methods were developed and validated for the determination of sertindole (SER) in the presence of its acid and oxidative degradates at λ(ex) 257 nm and λ(em) 335 nm. Method A was based on measuring the native fluorescence of SER using isopropanol as solvent. Method B was based on the enhancement of native fluorescence of SER quenched in aqueous media by using micellar microenvironment created by sodium dodecyl sulfate (SDS) anionic micelles using Britton Robinson Buffer (BRB) pH3.29 as solvent. Different factors affecting fluorescence intensity; both native and enhanced, were carefully studied to reach the optimum conditions of measurements. The proposed spectrofluorimetric methods were validated in accordance with ICH guidelines and were successfully applied for the determination of SER in bulk powder and pharmaceutical preparation with high sensitivity and stability indicating power. They were also statistically compared to the manufacturer methods with no significant difference in performance., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Four native fluorescence methods were suggested for simultaneous determination of amlodipine (AML) and valsartan (VAL). These methods were based on excitation of both drugs at λ(ex) 300 nm, in one step, to give maximum emission at λ(em) 378 and 496 nm for AML and VAL, respectively. The first method, single λ(ex) method, was used without any additions. The sensitivity of this method was further increased by the addition of hydroxy propylmethyl cellulose (HPMC) surfactant, β-cyclodextrin, or ferric oxide magnetite nanoparticles, in the other three methods. Different types of surfactants, and different concentration levels of both β-cyclodextrin and ferric oxide nanoparticles, were scanned to determine the optimum conditions for enhancing the sensitivity. Some factors affecting the fluorescence intensity of both cited drugs, like the type and volume of the added solvent (to be used as a sensing agent), and pH of measurement were studied and optimized. The proposed methods could be used in determination of AML and VAL in bulk powder, their laboratory prepared mixtures and pharmaceutical formulations. The obtained results were statistically compared to each other and to that of some reported methods. The specificity of the developed methods was investigated, and the methods were validated according to ICH guidelines., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Solid-liquid extraction, ultrasonic-assisted extraction and matrix solid-phase dispersion (MSPD) were optimized and compared in terms of recoveries for the simultaneous extraction of indole (IND) and 2,4-dichlorophenol (DCP) from catfish samples and for the extraction of IND alone from potato samples. Applying high-performance liquid chromatography (HPLC-DAD) procedure using mobile phase of methanol : water (65 : 35) at 280 nm, MSPD was the method of choice for the extraction of IND and DCP from catfish and, also, for IND from potato. The extraction recoveries of MSPD were in the range (97.9-99.7%) and (99.8-100.6%); for IND and DCP, respectively, in catfish samples and (98.4-99.7%) for IND alone in potato samples. Solid-phase extraction (SPE) was chosen the method of choice for the extraction of DCP from fish farms water samples after optimization and comparison with direct sample injection and extraction recoveries were in the range (97.9-100.3%). Kinetics were further studied to follow each of production of IND in catfish during storage at different temperatures and uptake of DCP by tilapia in fish farms water samples using MSPD-HPLC and SPE-HPLC, respectively., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

An accurate and sensitive synchronous spectrofluorimetric method has been developed for the determination of Polymyxin B sulphate (Poly B) in human plasma. The method is based on the reaction of non-fluorescent Poly B with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7 producing a yellow color with maximum relative fluorescence at 440 nm using a constant wavelength difference Δλ = 80 nm. Reaction conditions and other analytical parameters were studied and optimized using factorial design. Three level factorial designs have been employed for the screening, optimization of all experimental variables and determination of their interactions on the final product formation. The variables under investigation were: pH of borate buffer, volume of buffer, volume of NBD-Cl, temperature, time of heating and volume of sulfuric acid. A linear plot between relative fluorescence and concentration was obtained over the concentration range 100.00-1200.00 ng mL(-1). The limit of detection (LOD) and limit of quantification (LOQ) were found to be 10.31 and 31.24 ng mL(-1), respectively. The proposed method was validated according to ICH guidelines and successfully applied for the determination of Poly B in human plasma, where satisfactory results were obtained. The results obtained were statistically compared with those of a published method, where no significant difference was observed.

Two sensitive and selective spectrofluorimetric methods are proposed to determine ethopabate (ETH) and amprolium hydrochloride (AMP). First derivative synchronous spectrofluorimetry determines the natively fluorescent ethopabate at 288 nm in presence of amprolium hydrochloride which is a non fluorescent quaternary compound with average recovery 100.54±0.721 over a concentration range of 0.01-0.8 μg/mL. Limits of detection (LOD) and quantification (LOQ) are 0.002 and 0.007 μg/mL, respectively. The second method is direct synchronous spectrofluorimetry for determining amprolium hydrochloride at 362 nm after a reaction with 5% NaOH and 0.08% potassium ferricyanide that is optimized by a two-level factorial design. This method is linear over a concentration range of 0.01-0.65 μg/mL with average recovery 99.4±1.28. Limits of detection (LOD) and quantification (LOQ) are 0.002 and 0.006 μg/mL, respectively. The proposed methods are found to be valid and applicable for the analysis of ETH and AMP in their veterinary formulation. They are successfully applied to determine the studied drugs in chicken plasma and their residues in chicken muscle, liver, egg and chicken-based baby food product with recoveries in the ranges of 95.71-108.73% and 97.36-111.89% and for ETH and AMP, respectively., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A modified dispersive liquid-liquid extraction (DLLE) procedure coupled with spectrophotometric techniques was adopted for simultaneous determination of naphthalene, anthracene, benzo(a)pyrene, alpha-naphthol and beta-naphthol in water samples. Two different methods were used, partial least-squares (PLS) method and a new derivative ratio method, namely extended derivative ratio (EDR). A PLS-2 model was established for simultaneous determination of the studied pollutants in methanol, by using twenty mixtures as calibration set and five mixtures as validation set. Also, in methanol a novel (EDR) method was developed for determination of the studied pollutants, where each component in the mixture of the five PAHs was determined by using a mixture of the other four components as divisor. Chemometric and EDR methods could be also adopted for determination of the studied PAH in water samples after transferring them from aqueous medium to the organic one by utilizing dispersive liquid-liquid extraction technique, where different parameters were investigated using a full factorial design. Both methods were compared and the proposed method was validated according to ICH guidelines and successfully applied to determine these PAHs simultaneously in spiked water samples, where satisfactory results were obtained. All the results obtained agreed with those of published methods, where no significant difference was observed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

New accurate, sensitive and selective spectrophotometric and spectrofluorimetric methods were developed and subsequently validated for determination of Cromolyn sodium (CS) and Oxymetazoline HCl (OXY) in binary mixture. These methods include 'H-point standard addition method (HPSAM) and area under the curve (AUC)' spectrophotometric method and first derivative synchronous fluorescence spectroscopic (FDSFS) method. For spectrophotometric methods, absorbances were recorded at 241.5nm and 274.9nm for HPSAM and the wavelength was selected in ranges 232.0-254.0nm and 216.0-229.0nm for AUC method, where the concentration was obtained by applying Cramer's rule. For FDSFS method, the first-derivative synchronous fluorescence signal was measured at 290.0nm, using Δλ=145.0nm. The suggested methods were validated according to International Conference of Harmonization (ICH) guidelines and the results revealed that they were precise and reproducible. All the obtained results were statistically compared with those of the reported method and there was no significant difference., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This work deals with spectrophotometric, spectrofluorimetric, and potentiometric analyses of cetyltrimethylammonium bromide (CTAB) cationic detergent. The spectrophotometric procedure depends on measuring the absorbance of its binary complex with eosin yellow in Britton-Robinson buffer (pH 4) at Lambda max 547 nm in the range of 2.0-14.0 microg/mL with an accuracy of 100.15 +/- 0.54%. The spectrofluorimetric procedure depends on determining the quenching of the fluorescence intensity of fluorescein dye by CTAB in the presence of borate buffer at Lambda em = 500 nm, Lambda ex = 304 nm, in the range of 2.90-14.50 microg/mL with an accuracy of 99.81 + 0.33%. The electrochemical procedure describes an ionophore-based technique using a graphite sensor to measure 0.036 microg/mL and showed an accuracy of 100.11 +/- 0.61%. The experimental conditions affecting each of the three suggested procedures were studied and optimized. All the developed procedures were validated and satisfactorily applied for the determination of CTAB in industrial wastewater samples.

A mixed micellar medium of sodium dodecyl sulfate and Pluronic F-127 was used to enhance the fluorescence of naphthalene and to obtain lower LODs. The method was based upon measuring the first-derivative synchronous fluorescence spectrum of naphthalene by using a mixed micellar medium at a constant wavelength difference delta lambda = 60 nm, where a greater fluorescence enhancement was observed if compared to using a single surfactant separately. A linear fluorimetric calibration curve was obtained for naphthalene in a concentration range of 10-200 ng/mL. The LOD was 7.13 ng/mL, which is well below the health advisory limit for naphthalene in drinking water as suggested by the U.S. Environmental Protection Agency. The method can be easily adopted for determination of naphthalene in aqueous media including tap water and river water. The recoveries obtained were 95.979-115.645%. The proposed method was validated according to International Conference on Harmonization guidelines and successfully applied to determine naphthalene in real life water samples from different sources.

A novel method could be adopted successfully for determination of anthracene in environmental samples, utilizing dispersive liquid-liquid extraction followed by first-derivative synchronous fluorimetry at a constant wavelength difference Δλ = 165 nm, where a linear calibration curve was obtained in a concentration range of 0.5-100 ng mL(-1) at 244 nm. The detection limit was 0.1 ng mL(-1). The method can be easily adopted for determination of anthracene in aqueous media including tap water and river water. The recoveries obtained were 85.40-108.02%. The proposed method was validated according to International Conference of Harmonization (ICH) guide lines and successfully applied to determine anthracene in pure form and in water samples including real life water samples from different sources. All the results obtained were compared with those of published method, where no a significant difference was observed.

Successfully benzo(a)pyrene could be quantitified in environmental samples by a novel synchronous spectrofluorimetric techniques at a constant wavelength difference Δλ = 120 nm, using beta-cyclodextrin 'β-CD' and calix(8)arene as fluorescence enhancers, where a linear calibration curve was obtained in a concentration range of 900-14,400 pg mL(-1) and 18-360 pg mL(-1) and the detection limit of 380.00 pg mL(-1) and 12.08 pg mL(-1) (which is well below the maximum contaminant concentration for benzo(a)pyrene set by the Environmental Protection Agency 'EPA') using both enhancers, respectively. The method can be easily adopted for determination of benzo(a)pyrene in aqueous media including tap water, river water and complex water samples. The recoveries obtained were 85.13-113.36 % with RSD < 4 %. The proposed method was validated according to International Conference of Harmonization (ICH) guide lines and successfully applied to determine benzo(a)pyrene in pure form and in water samples including contaminated environmental water samples. All the results obtained were compared with those of a published method, where no significant difference was observed.

Three novel neostigmine bromide (NEO) selective electrodes were investigated with 2-nitrophenyl octyl ether as a plasticiser in a polymeric matrix of polyvinyl chloride (PVC). Sensor 1 was fabricated using tetrakis(4-chlorophenyl)borate (TpClPB) as an anionic exchanger without incorporation of an ionophore. Sensor 2 used 2-hydroxy propyl β-cyclodextrin as an ionophore while sensor 3 was constructed using 4-sulfocalix-8-arene as an ionophore. Linear responses of NEO within the concentration ranges of 10(-5) to 10(-2), 10(-6) to 10(-2) and 10(-7) to 10(-2) mol L(-1) were obtained using sensors 1, 2 and 3, respectively. Nernstian slopes of 51.6 ± 0.8, 52.9 ± 0.6 and 58.6 ± 0.4 mV/decade over the pH range of 4-9 were observed. The selectivity coefficients of the developed sensors indicated excellent selectivity for NEO. The utility of 2-hydroxy propyl β-cyclodextrin and 4-sulfocalix[8]arene as ionophores had a significant influence on increasing the membrane sensitivity and selectivity of sensors 2 and 3 compared to sensor 1. The proposed sensors displayed useful analytical characteristics for the determination of NEO in bulk powder, different pharmaceutical formulations, and biological fluids (plasma and cerebrospinal fluid (CSF)) and in the presence of its degradation product (3-hydroxyphenyltrimethyl ammonium bromide) and thus could be used for stability-indicating methods., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Three sensitive, selective, and precise stability-indicating methods for the determination of the novel osteoarthritis drug, diacerein (DIA) in the presence of its alkaline degradation product (active metabolite, rhein) and in pharmaceutical formulation were developed and validated. The first method is a first derivative (D(1) ) spectrophotometric one, which allows the determination of DIA in the presence of its degradate at 322 nm (corresponding to zero crossing of the degradate) over a concentration range of 4-40 µg/mL with mean percentage recovery 100.21 ± 0.833. The second method is the first derivative of the ratio spectra (DD(1) ) by measuring the peak amplitude at 352 nm over the same concentration range as (D(1) ) spectrophotometric method, with mean percentage recovery 100.09 ± 0.912. The third method is a TLC-densitometric one, where DIA was separated from its degradate on silica gel plates using ethyl acetate:methanol:chloroform (8:1.5:0.5 v:v:v) as a developing system. This method depends on quantitative densitometric evaluation of thin layer chromatogram of DIA at 340 nm over a concentration range of 1-10 µg/spot, with mean percentage recovery 100.24 ± 1.412. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of DIA in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with reference method., (Copyright © 2010 John Wiley & Sons, Ltd.)

Three sensitive, selective and precise stability-indicating methods for the determination of the anti-Alzheimer's drug, rivastigmine hydrogen tartrate (RIV) in the presence of its alkaline degradation product (major metabolite, NAP 226-90) and in pharmaceutical formulation were developed and validated. The first method is a second derivative (D(2)) spectrophotometric one, which allows the determination of RIV in the presence of its degradate at 262 nm (corresponding to zero crossing of the degradate) over a concentration range of 50-500 microg/ml with mean percentage recovery 100.18 +/- 0.628. The second method is the first derivative of the ratio spectra (DD(1)) by measuring the peak amplitude at 272 nm over the same concentration range as (D(2)) spectrophotometric method, with mean percentage recovery 99.97 +/- 0.641. The third method is a TLC-densitometric one, where RIV was separated from its degradate on silica gel plates using methanol:butanol:H(2)O:ammonia (5:4:1:0.01 v:v:v) as a developing system. This method depends on the quantitative densitometric evaluation of thin layer chromatogram of RIV at 263 nm over a concentration range of 20-160 microg/spot, with mean percentage recovery 100.19 +/- 1.344. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of RIV in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with reference method.

Two pyridostigmine bromide (PB) selective electrodes were investigated with 2-nitrophenyl octyl ether as a plasticizer in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH), based on the interaction between the drug solution and the dissociated COOH groups in the PVC-COOH. One of the sensors was fabricated by using PVC-COOH only as anionic site without incorporation of an ionophore (sensor 1). The second sensor was constructed by using 2-hydroxy propyl beta-cyclodextrin as an ionophore (sensor 2). Linear responses of PB within a concentration range of 10(-3)-10(-2) and 10(-5)-10(-2) M, with slopes of 51.9 +/- 0.31 and 56.7 +/- 0.40 mV/decade over pH range of 5-10 were obtained using sensors 2 and 1, respectively. The proposed method displayed useful analytical characteristics for determination of PB in tablets with average recoveries of 100.22 +/- 0.62, and 100.15 +/- 0.72, and in plasma with average recoveries of 99.14 +/- 1.19 and 99.79 +/- 0.72, for sensors 2 and 1, respectively. The utility of 2-hydroxy propyl beta-cyclodextrin as an ionophore has a significant influence on increasing both membrane sensitivity and selectivity of sensor 2 in comparison with sensor 1. The methods were also used to determine the intact drug in the presence of its degradate, and thus could be used as stability-indicating methods. The results obtained by the proposed procedures were statistically analyzed and compared with those obtained by the U.S. Pharmacopeia method. No significant difference for either accuracy or precision was observed.

Novel miniaturized polyvinyl chloride (PVC) membrane sensors in all-solid state graphite and platinum wire supports were developed, electrochemically evaluated and used for the assay of rivastigmine hydrogen tartrate drug (RIV). The RIV sensors are based on the formation of an ion-association complex between the drug cation and tetrakis(4-chlorophenyl)borate (TpClPB) anionic exchanger as electroactive material dispersed in a PVC matrix. Linear responses of 10(-2) - 10(-5) M and 10(-2) - 10(-4) M with cationic slopes of 56.4 mV and 53.6 mV over the pH range 4 - 7 were obtained by using the RIV-coated graphite (sensor 1) and platinum wire (sensor 2) membrane sensors, respectively. The proposed method displays useful analytical characteristics for the determination of RIV in Exelon capsules with average recoveries of 100.01+/-0.835, 100.09+/-0.896, and in plasma with average recoveries of 99.47+/-0.97, 99.58+/-0.82, and in rat brain homogenate with average recoveries of 98.16+/-1.62, 99.02+/-1.57, for sensors 1 and 2, respectively. The methods were also used to determine the intact drug in the presence of its degradation product and thus could be used as stability indicating methods. The results obtained by the proposed procedures were statistically analyzed and compared with those obtained by using a reported method. No significant difference for both accuracy and precision was observed.

The construction and electrochemical response characteristics of beta-cyclodextrin-based sensor for determination of the amino glycosidic antibiotic, tobramycin, is described. The membrane incorporates carboxylated poly (vinyl chloride) as matrix polymer, tetrakis-fluorophenyl borate as fixed anionic site and nitrophenyloctylether as plasticizer. The uptake of aminoglycosidic drug was applied to determine permeability changes in the Gram-negative bacteria Escherichia coli as test organism and ethylenediamine tetraacetic acid as model permeabilizer. The sensor shows linear response over concentration range of 10(-2) to 10(-5)M tobramycin with cationic slope of mV per concentration decade and accuracy of 99.8+/-2.14%. The proposed method was successfully applied to the determination of tobramycin uptake, by 100 microl E. coli suspension in presence of up to 10 microg ml(-1) of EDTA solution, with average recovery of 99.3+/-2.77%. The obtained results were compared reasonably well with the data obtained using the compendial fluorimetric assay. The proposed potentiometric assay serves as a convenient method in analyzing and quantifying the effects of permeabilizers on Gram-negative bacteria upon treatment with tobramycin.

Four glutathione (GSH)-selective electrodes were developed with different techniques and in different polymeric matrices. Precipitation-based technique with bathophenanthroline-ferrous as cationic exchanger in polyvinyl chloride (PVC) matrix was used for sensor 1 fabrication. beta-Cyclodextrin (beta-CD)-based technique with either tetrakis(4-chlorophenyl)borate (TpClPB) or bathophenanthroline-ferrous as fixed anionic and cationic sites in PVC matrix was used for fabrication of sensors 2 and 3, respectively. beta-CD-based technique with TpClPB as fixed anionic site in polyurethane (Tecoflex) matrix was used for sensor 4 fabrication. Linear responses of 1x10(-5) to 1x10(-4)M and 1x10(-6) to 1x10(-3)M with slopes of 37.5 and 32.0mV/decade within pH 7-8 were obtained by using electrodes 1 and 3, respectively. On the other hand, linear responses of 1x10(-5) to 1x10(-2) and 1x10(-5) to 1x10(-3)M with slopes of 47.9 and 54.3mV/decade within pH 5-6 were obtained by using electrodes 2 and 4, respectively. The percentage recoveries for determination of GSH by the four proposed GSH-selective electrodes were 100+/-1, 100.5+/-0.7, 100+/-1 and 99.0+/-0.8% for sensors 1, 2, 3 and 4, respectively. Determination of GSH in capsules by the proposed electrodes revealed their applicability for determination of GSH in its pharmaceutical formulations. Also, they were used to determine GSH selectively in presence of its oxidized form (GSSG). Sensor 4 was successfully applied for determination of glutathione in plasma with average recovery of 100.4+/-1.11%. The proposed method was compared with a reported one. No significant difference for both accuracy and precision was observed.

The construction and electrochemical response characteristics of poly (vinyl chloride) matrix membrane sensors for seven phenolic compounds (phenol, o-cresol, p-cresol, p-chlorophenol, o-nitrophenol, alpha-naphthol and beta-naphthol) are described. The membranes incorporate ion association complexes of these seven phenolic anions with phenanthroline-iron(II) as electroactive materials. These sensors show linear response for phenol, o-cresol, p-cresol, p-chlorophenol, o-nitrophenol, alpha-naphthol, and beta-naphthol over wide concentration ranges, with an average anionic slope 54.3 mV per concentration decade. The suggested sensors exhibit fast response time (1 min), low determination limits (1 x 10(-5)M), good stability (2-3 weeks), reasonable selectivity to phenolic compounds in the presence of other water pollutants. The average percentage recovery was 99.78+/-0.088 for individual phenolates and 99.61+/-0.198 for phenolates in mixtures. The investigated sensors were successfully used for direct potentiometric determination of traces of these phenolic compounds in wastewater samples. Results with mean accuracy of 99.74+/-0.29%, 99.82+/-0.36%, 99.65+/-0.47%, 99.73+/-0.37%, 99.77+/-0.30%, 99.86+/-0.31% and 99.91+/-0.22% was obtained for the seven sensors, respectively. These results were compared with data obtained using the British pharamacopial method (The British Pharmacopoeia, Her Majesty's Stationary Office, London, 1993) and others (Clarke's Isolation and Identification of Drugs in Pharmaceuticals Body Fluids and Post-mortem Materials, 2nd Edition, The Pharmaceutical Press, London, 1998).

Two hydroxyurea selective electrodes were investigated with beta-cyclodextrin used as ionophore and either tetrakis (p-chlorophenyl) borate (electrode 1), or tetrakis [3,4-bis (trifluoromethyl) phenyl] borate (electrode 2), as a fixed anionic site in a polymeric matrix of carboxylated polyvinyl chloride. Linear responses of hydroxyurea within a concentration range of 10(-5)-10(-)3 M with slopes of 51.2 and 58.6 mV/decade with pH 3-6 were obtained by using electrodes 1 and 2, respectively. Two spectrofluorimetric methods involving the formation of drug-AI(III) complex (method 3) and drug-Mg(II) complex (method 4) at pH 5 were also investigated. These complexes emit fluorescence at wavelengths of 380 and 355 nm, after excitation at 305 nm, for AI and Mg complexes, respectively. The calibration graphs were rectilinear from 0.5 to 2.5 microg/mL for the AI complex and 1 to 5 microg/mL for the Mg complex. The 4 proposed methods display useful analytical characteristics for determination of hydroxyurea, with average recoveries of 100.2 +/- 0.83 and 99.4 +/- 1.81% in capsules and 99.7 +/- 0.70 and 99.4 +/- 1.25% in biological fluids for the potentiometric and fluorimetric methods, respectively. Results obtained by the proposed procedures were statistically analyzed and compared with those obtained by the U.S. Pharmacopeial method. The 4 proposed procedures were also used to determine the stability of the drug in the presence of its degradate, hydroxylamine.

The construction and electrochemical response characteristics of four polyvinylchloride (PVC) membrane sensors for the determination of monensin (MN) and salinomycin (SL) were described. The membranes were prepared using 1 wt.% drug, 44 wt.% nitrophenyl octyl ether, 53 wt.% PVC and 2 wt.% lipophilic additive which is the anionic potassium tetra (4-chlorophenyl) borate in sensors 1 and 2 and the cationic nicklo-phenanthroline in sensors 3 and 4. Sensor 1 and sensor 2 show linear responses over concentration range of 10(-3)-10(-5) M drug with cationic slopes of 52.3 and 54.1 mV per concentration decade, respectively. On the other hand sensor 3 and sensor 4 show linear responses over concentration range 10(-4)-10(-5) M drug with anionic slopes of 28.1 and 29.7 mV per concentration decade, respectively. The 4 sensors were successfully applied to the determination of MN and SL in their pharmaceutical products (Premix) with average recoveries of 98.4-100.4+/-2.41-1.97% for sensors 1 and 2 and 97.6-98.8+/-3.16-3.07% for sensors 3 and 4. The obtained results were compared reasonably well with the data obtained using the USP method (2000). The proposed sensors were also applied for the direct determination of both drugs in animal feed preparations without prior treatment in low levels; 10-1000 microg per 5 g feed. The sensors were successfully used to follow up the drugs concentration in the presence of other growth promotors, other antibiotics and the coexisting fatty acids.

The construction and electrochemical response characteristics of poly (vinyl chloride) and poly (vinyl chloride) carboxylate membrane sensors for the determination of cyclophosphamide and ifosphamide are described. Based on the formation of an ion-pair complex between the drug cation and sodium tetraphenylborate, two poly (vinyl chloride) sensors, namely a cyclophosphamide membrane sensor and ifosphamide membrane sensor were fabricated. They show a linear response for both drugs over the concentration range 10(-2)-10(-4) M with cationic slopes of 56 and 54.6 mV per concentration decade, for sensor 1 and sensor 2, respectively. Based on the interaction between the drug solution and the dissociated COOH groups in the poly (vinyl chloride) carboxylate, sensor 3 was fabricated. It shows a linear response for both drugs over the concentration range 10(-3)-10(-5) M with a cationic slope of 49.7 mV per concentration decade. The direct potentiometric determination of cyclophosphamide and ifosphamide in their pharmaceutical preparations using the proposed sensors gave average recoveries of 101.3+/-0.6, 100.8+/-10.7 and 102.0+/-11.0% for the sensors 1, 2 and 3, respectively, which compares reasonably well with the data obtained using the British Pharmacopoeial method (1993). Sensors 1 and 2 were also used to follow up the stability of the drugs studied in the presence of their degradates. These degradation products have no diverse effect on the responses of sensors 1 and 2.

Three reliable spectrophotometric and spectrofluorimetric procedures are described for the determination of fluorouracil in bulk powder and ampoules in the presence of its degradation products. One spectrophotometric procedure, based on measurement at 555 nm of the violet-coloured complex formed by fluorouracil with cobalt(II), has a detection limit of 0.03 mg mL(-1). Two sensitive spectrofluorimetric procedures are also proposed. One is based on measurement of the intrinsic fluorescence of the liberated fluorouracil at 375 nm, after precipitation as its cobalt(II) complex, decomposition of the precipitate with sulphuric acid and excitation at 295 nm. The second depends on excitation of the fluorouracil-cobalt(II) complex at 395 nm and measuring its fluorescence at 483 nm. The limits of detection of the two spectrofluorimetric procedures are 0.5 and 2 microg mL(-1), respectively. The three procedures have been used successfully for the determination of fluorouracil ampoules. The validity of the methods has been assessed by applying the standard addition technique.