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A new, sensitive, stability-indicating reversed-phase HPLC method was validated and applied for the simultaneous quantitation of sodium valproate and two paraben preservatives; methylparaben, and propylparaben in the liquid dosage form. Stability tests were carried out through exposure of the analyte's solution to stress conditions. Separation of the analytes was achieved on (waters) C18 Column (150 mm × 3.9 mm, 5 μm). A mixture of 0.05 M monobasic potassium phosphate pH 3.5 and acetonitrile (50:50; v/v) was applied at 1.5 ml/min flow rate and UV detection wavelength at 210 nm. The degradation products and the analytes were completely separated. The linearity was performed in the range of 50–150 % from a target concentration of 10 μg/ml propylparaben, 90 μg/ml methylparaben, and 2.88 mg/ml sodium valproate with a coefficient correlation (R2) 1.0 for methylparaben, propylparaben and sodium valproate. The validation results of the suggested method were in a good agreement with ICH guidelines. Application of the proposed method for analysis of liquid dosage forms was successfully carried out in the routine quality control process.

Gatifloxacin is the drug of choice in the treatment of community-acquired pneumonia in many studies. However, cytotoxicity was reported at its high doses. Therefore, gatifloxacin overdose monitoring is very important. In this sense, there is a need for developing fast and cheap analytical methods for gatifloxacin quantitation in biological fluids. In the present study, a novel detection strategy involving gatifloxacin quantification in urine samples was developed. The approach has been adapted for the use of solid inner contact and rapid disposal screen-printed graphitic carbon electrodes exhibiting high sensitivity toward gatifloxacin without interference from several ions found in urine samples. The developed electrodes showed linear responses in the concentration ranges from 1 × 10–5 to 0.01 and 1 × 10–6 to 0.01 M for a solid contact glassy carbon ion selective electrode (GSC) and a screen printed electrode (GSP), respectively. The analytical applicability of the approach was demonstrated through recovery experiments of gatifloxacin trace concentrations in urine. GSP ion selective electrode (ISE) was found to have superior stability, shorter response time, higher selectivity and sensitivity and longer shelf life compared to GSC ISE. GSP ISE showed the best Nernestian slope as well as the lowest detection limit. Moreover, the inherent advantages of screen-printed electrodes technology (low sample consumption, low cost and point of care testing) make this methodology very attractive in this field. As a result, the developed ISEs can be the best choice for in-line determination of gatifloxacin in urine samples to detect overdose intake and its associated symptoms as well as for quality-control laboratories without pre-treatment or separation steps.

We simultaneously determined tinidazole (TIN), miconazole nitrate (MIC), propylparaben (PP), and methylparaben (MP) using response surface and tolerance analysis approach. The selected critical to quality characteristics (CTQs) were tailing factor (Tf), resolution between peaks (Rs), and number of plates (N). The gradient steepness (ΔG) and, the column oven temperature were the critical to process characteristics (CTPs). The chromatographic separation was on a C18 column with a gradient elution program using methanol as organic modifier and 10 mM sodium acetate buffer (pH 4.9) as the aqueous part of the mobile phase at 2 ml/min flow rate, with UV detector at 235 nm and, a column oven temperature of 34.5 °C. SFSTP guidelines were used to validate the method; it was accurate over the concentration range of 18.75–150, 2.5–20 and 12.5–100 μg ml−1 for TIN, MP, PP, and MIC, respectively.

Novel univariate and multivariate factor-based calibration-prediction techniques were validated for simultaneous ultraviolet spectrophotometric determination of ribavirin (RIV), daclatasvir (DAV), sofosbuvir (SOV), and sorafenib (SON) which are co-administered for treatment of hepatocellular carcinoma (HCC) that results from Hepatitis C-virus (HCV) infection in their commercial products and in biological fluids. Determination of these compounds is essential owing to their pharmacotherapeutic benefits. Due to spectral overlapping of RIV, DAV, SOV, and SON, univariate extended derivative ratio (EDR) method and multivariate partial least-squares (PLS) and principal component regression (PCR) methods were used for constructing the calibration curves. The extended derivative ratio (EDR) absorption maxima at 215 nm and minima at 310.5 nm was used for determination of RIV and DAV, respectively and absorption maxima at 240.3 nm and minima at 284.5 nm for determination of SOV and SON, respectively. The linearity was established over the range of 6–42 μg mL−1, 4–16 μg mL−1, 10–70 μg mL−1, and 3–9 μg mL−1 for RIV, DAV, SOV and SON with correlation coefficient (r2) of 0.9997, 0.9997, 0.9999 and 0.9997, respectively. This method was effectively applied to pure, pharmaceutical preparations and to spiked human urine and plasma. PLS and PCR models were established for the determination of the studied drugs in the range of 6–42, 4–16, 10–70 and 3–9 μg mL−1 for RIV, DAV, SOV, and SON, respectively. Furthermore, updating the PLS model (PLS model update) were allowed for the determination of these drugs in spiked human urine, plasma and drug-dissolution test of their tablets. The obtained results were compared to official and reported method showing that there were no significant differences. The results of applying PLS and PCR models for evaluation of RIV, DAV, SOV, and SON in human urine samples as real samples were also encouraging. It is expected that the suitable features of the proposed method make it helpful for biological and clinical applications.

Cold is a leading cause of school and work absenteeism. Most cold over-the-counter medicines (OTC) contain paracetamol (PA), guaifenesin (GU) and other active ingredients. Ascorbic acid (AS) in pharmaceutical preparations is designed for preventing and treating respiratory viral infections. Thus, we report a robust voltammetric method for simultaneous determination of AS, PA and GU in their effervescent dosage form. The advantages of nanotechnology and chemometrics were combined to enhance the performance of electroanalysis. Fractional factorial design (FrFD) and dual response surface method (DRSM) were sequentially conducted. The method was validated in agreement with ICH guidelines; it showed accuracy over the concentration range of 11.3–108.9, 14.6–140.3, 4.6–43.9 μg ml−1 for AS, PA and GU, respectively. Based on findings, a robust and not time-consuming procedure was applied.

We report a robust HPLC-UV method for ascorbic acid (AS), paracetamol (PA) and guaifenesin (GU) based on response surface/tolerance analysis approach to meet Six Sigma quality of the performance of a chromatographic method. Our goals were the bringing specifications into the optimizations and achieving robustness during the development phase. The critical method attributes (CMAs) were resolution between the peak pairs (Rs), the analysis time(T), tailing factor (Tf), number of theoretical plates (N), and back pressure(P).The critical method parameters (CMPs) included a percentage of organic modifier, a flow rate of the mobile phase, and a temperature of column oven. The separation was performed on a CN column, using an isocratic mode with a mixture of 50 mM potassium dihydrogen phosphate buffer adjusted with ortho-phosphoric acid to pH 2.2 as the aqueous component of the mobile phase and methanol in the ratio 85.9:14.1 (v/v) at 1 ml/min flow rate, with UV detector at 275 nm and a column temperature of 45 °C. The method was validated using the accuracy profiles. Finally, the method was applied to pharmaceutical dosage form.

An easy, quick, simple and accurate spectrofluorimetric method was recognized and validated for evaluation of sorafenib (SOR) in pure form and biologically in plasma. Cremophor RH 40 (Cr RH 40) used for enhancing the fluorescence activity of SOR in phosphate buffer (pH 7). Cr RH 40 improved the native fluorescence of SOR remarkably in water. The fluorescence spectrum of SOR was observed at 405 nm after excitation at 265 nm. The linearity appeared to be in the range of 5 to 600 ng ml−1 for pure and from 9 to 500 ng ml−1 for plasma using the protein precipitation (ppt) method while from 10 to 500 ng ml−1 for plasma using liquid–liquid extraction method. The precisions and the accuracy of the estimated method gave satisfactory results. The recommended method was effectively applied for determination of SOR in human plasma with high recovery values. The results of some compounds that are possibly found in plasma were studied. The proposed method was also focused on real volunteers and a drug dissolution test.

The data presented are related to the article entitled “Six Sigma quality approach for HPLC-UV method optimization” Ibrahim et al., 2019. The raw data of HPLC analysis of ascorbic acid (AS), paracetamol (PA) and guaifenesin (GU) are presented. Calibration standards were prepared at six concentrations levels (25%, 50%, 75%, 100%, 125% and 150%) each day and measured in triplicate. Validation standards were prepared at four concentration levels (25%, 60%, 100% and 150%) each day and measured in quintet. Three different series were used for method validation and prepared at the rate of one series per day. Keywords: Accuracy profile, HPLC, Ascorbic acid, Paracetamol, Guaifenesin

Objective: Simple, rapid and reproducible reversed-phase high performance liquid chromatography (RP-HPLC) and ultraviolet derivative spectrophotometric (UVDS) methods for the simultaneous determination of daclatasvir (DAC) and sofosbuvir (SOF) in pure and in pharmaceutical dosage forms have been developed and validated. Methods:The chromatographic separation of DAC and SOF was achieved using Agilent Zorbax SB C18 (4.6 x 250 mm, 5 μm) column at temperature of 40 °C. The mobile phase used was 9 mM dipotassium hydrogen orthophosphate buffer (pH 4±0.1): acetonitrile (60:40, v/v). The flow rate was maintained at 1 mL/min with UV detection at 265 nm. Results: The calculated resolution was 4.56 (> 2), which ensures complete separation. The tailing factor was 1.13 and 1.40 (≤ 2) for DAC and SOF, respectively. Intermediate precision value was ≤ 2% indicate acceptable ruggedness. Conclusion: The two methods were validated according to the International Conference on Harmonization (ICH) guidelines in terms of linearity, precision, accuracy, selectivity, specificity, detection limit, quantification limit, robustness and ruggedness.

Counterfeit drugs have adverse effects on public health; chromatographic methods can be used but they are costly. In this study, we developed cost-effective and environmentally friendly methodology for the analysis of terazosin HCl (TZ) in the presence prazosin hydrochloride (PZ) using UV spectroscopy in conjunction with machine learning (ML) models. Variable selection algorithms were applied to select most informative spectral variables. Thirty-five ML models were assessed and their performances were compared. The models covered a wide range of prediction mechanisms, such as tree-based, linear, self-organizing maps, neural network, Gaussian process, boosting, bagging, Bayesian models, kernel methods, and quantile regression. The values of the root mean square error (RMSE), coefficient of determination (R2), and absolute mean error (MAE) were obtained for the evaluation of the developed models. According to the results of these performance indices, linear model showed the highest prediction capacity among all other models. RMSE, R2 and MAE values of (0.159, 0.997 and 0.131) and (0.196, 0.99 and 0.161) were obtained for train and test datasets, respectively. The predictive models in this study can be useful for the researchers who are interested to work on the determination of active ingredients in pharmaceutical dosage forms in the presence of interference using UV spectroscopy; therefore, it was used to determine TZ without interference of PZ.

A simple RP-HPLC-PDA method for determination of atenolol (ATN) and trimetazidine (TMZ) in human urine and tablets has been developed. Analytes were separated on a Caltrex BI column (125× 4.0 mm, 5 μm) with 25mM potassium dihydrogen phosphate pH 3.3, methanol, and acetonitrile mobile phases. The PDA detector was operated at 210 nm for TMZ and 225 nm for ATN and the flow rate was 1.0 mL/ min. Linearity was obtained over a concentration range of (1.0-100 μg/mL) for both analytes in standard solutions and the method was successfully applied for determination of target analytes in their pharmaceutical tablets. Excellent linearity was also obtained over concentration ranges of (0.25-25 μg/mL) and (0.5-25 μg/mL) in human urine for TMZ and ATN, respectively. A simple liquid-liquid extraction was applied for urine sample clean-up and a gradient method was used for chromatographic separation. The lower limit of quantitation (LOQ) was 0.99 and 0.60 μg/mL for ATN and TMZ, respectively. The limit of detection (LOD) was 0.30 and 0.18 μg/mL for ATN and TMZ, respectively. Inter- and intraday precision and accuracy for ATN were within ±1.89% in pure form and within ±2.85% in urine samples. Inter- and intraday precision and accuracy for TMZ were within ± 3.99% in pure form and within ± 3.19% in urine samples.

The oxidation of itraconazole at three different electrodes; ultra-trace graphite (UTGE), pencil graphite (PGE) and carbon paste (CPE) electrodes were studied voltammetrically. After the optimization of solution pH, accumulation potential and accumulation time, anodic stripping differential pulse and anodic stripping square wave voltammetric peaks were obtained. The oxidation mechanism was proposed. Based on these findings, a simple and not time-consuming procedure was successfully applied for the determination of itraconazole in pharmaceutics and biological fluids.

Simultaneous determination of sofosbuvir (SOF), and daclatasvir (DAC) in their dosage forms, human urine and human plasma using simple and rapid micellar high performance liquid chromatographic method coupled with UV detection (HPLC-UV) had been developed and validated. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of Hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. Separation and quantitation were carried out on anonyx™ C8 monolithic (100 × 4.6 mm (i.d.) analytical column maintained at 25 °C. The mobile phase consisted of 0.1 M sodium dodecyl sulfate (SDS) solution containing 20% (V/V) n-propanolol and 0.3% (V/V) triethylamine and pH was adjusted to 6.5 using 0.02 M phosphoric acid, respectively. The retention times of SOF and DAC were 4.8 min, and 6.5 min, respectively. Measurements were made at flow rate of 0.5 mL/min with injection volume of 20 μL and ultraviolet (UV) detection at 226 nm. Linearity of SOF and DAC was obtained over concentration ranges of 50–400, and 40–400 ng/mL, respectively in pure form, 60–300 and 50–300 ng/mL, respectively for human plasma and over 50–400, and 40–400 ng/mL, respectively for human urine with correlation coefficient >0.999. The proposed method demonstrated excellent intra- and inter-day precision and accuracy. The suggested method was applied for determination of the drugs in pure, dosage form, and in real human plasma, real human urine and drug-dissolution test of their tablets. The obtained results have been statistically compared to reported method to give a conclusion that there is no significant differences.

The following paper represents a simple, highly sensitive, responsive validated and developed spectrofluorimetric method for estimation of imatinib (IMB) in its pure, commercial preparation, human urine and human blood plasma. The calibration curve was in the range 4-900 ng ml-1 for pure form and urine and 8-900 ng ml-1 for plasma in a medium contains carboxymethyl cellulose (CMC) and acetate buffer (pH 5) with excitation wavelength (λex ) 230 nm and emission wavelength (λem ) 307 nm. The limit of detection (LOD) was 0.37 ng ml-1 for the pure form, 0.64 ng ml-1 for human urine, and 0.70 ng ml-1 for human plasma, while the limit of quantitation (LOQ) was 1.2 for pure form, 1.91 for urine and 2.1 for plasma. The suggested method was successfully applied for evaluation of IMB in tablets within 99% mean percentage recovery. The excipients that are usually used as additives in pharmaceutical dosage form did not interfere with the suggested method. The method was efficiently used for estimation of IMB in human urine and human plasma. The effect of some cations that might be present in urine and plasma was also studied. The method was also focused on human volunteers and in vitro drug release.

Two novel and sensitive methods for quantitative determination of doxycycline hyclate and oxytetracycline HCl were developed. The first method (method A) is based on the reducing character of the cited drugs which causes chemical reduction of silver ions to silver nanoparticles (Ag-NPs) in the presence of polyvinyl pyrrolidone (PVP) as a stabilising agent producing surface plasmon resonance which has absorption peaks at 424 and 428 nm for doxycycline hyclate and oxytetracycline HCl, respectively. The nanoparticles were characterised by UV-VIS spectrophotometry and transmission electron microscopy (TEM). The plasmon absorbance of the Ag-NPs was used for the quantitative spectrophotometric determination of the cited drugs. The second method (method B) is a conductometric method which is based on the reaction of the cited drugs with phosphotungstic acid to form ion associates in aqueous system. Validation of the proposed methods was carried out.

New, sensitive, and selective spectrophotometric and spectrofluorometric methods have been developed for determination of clemastine hydrogen fumarate (Clem), loratadine (Lor), losartan potassium (Los), and ramipril (Ram) in both pure form and pharmaceutical formulations using 4-chloro-7-nitrobenzofurazan (NBD-Cl), which is a highly sensitive chromogenic and fluorogenic reagent. The relation between absorbance at 470, 467, 471, and 469 nm and the concentration was linear over the ranges 5–35, 10–100, 10–90, and 10–120 μg/mL for Clem, Lor, Los, and Ram, respectively. The complexation products were also measured spectrofluorometrically at the emission wavelength 535 nm for Clem, Lor, and Ram and at 538 nm for Los with excitation at 477 and 452 nm for Clem and Lor, respectively, and 460 nm for both Los and Ram. The fluorescence intensity was directly proportional to the drug concentration over the ranges 0.05–0.5, 5–20, 1–6, and 2–15 μg/mL for Clem, Lor, Los, and Ram, respectively. The methods were successfully applied for the determination of the studied drugs in pharmaceutical dosage forms with excellent recovery.

Objective The aim of the present work was to develop simple spectrophotometric methods for the simultaneous determination of bambuterol hydrochloride. Method Spectrophotometric method for determination of bambuterol hydrochloride after its conversion to bambuterol base by formation of charge transfer complexes as n-donor with π-acceptors, dichlorodicyanobenzoquinone (DDQ) and tetracyanobenzoquinodimethane (TCNQ) which were prepared in acetonitrile. They yield radical anions measured at 461 and 842 nm within concentration ranges of 36.7–183.7, 4.59–36.7 μg ml−1 with a good correlation coefficients (r2 = 0.9999–0.9998) respectively. The nature of the formed complexes was studied via determination of the association constant and the molar absorptivity using Bensi–Hildebrand equation. The free energy change (ΔG) and the enthalpy of formation (ΔH) as well as the entropy (ΔS) were determined for the reaction product with TCNQ. The method was successfully applied for the analysis of bambuterol hydrochloride in its pharmaceutical preparation where no interference could be observed from the additives commonly present as proven by good mean recoveries of 99.74% and 100.014%. There was no significant difference observed when the method was statistically compared with the pharmacopeial official method used for determination. Conclusion The proposed charge transfer complexation methods are rapid and simple and from the economical point of view, the analytical reagents used are inexpensive, have excellent shelf life and are available in any analytical laboratory. The suggested methods could be successfully applied for quality control and routine analysis.

Simple, accurate, precise, and rapid extractive spectrophotometric method was developed for the estimation of gatifloxacin (I) and cefotaxime sodium (II) in both pure and pharmaceutical dosage forms. The method was based on the formation of colored complex by the drugs with Eriochrome black-T in an acidic medium. The ion-associated complex formed was quantitatively extracted under the experimental conditions with methylene chloride and the absorbances of the organic layers were measured at 510 nm. Beer’s law was obeyed in the concentration range of (318) and (30-120) ig.ml -1 for drug (I) and (II) respectively .The correlation coefficient (r 2 ) for the studied drugs was found to be 0.9999. The molar absorptivity (µ), sandell sensitivity, detection (LOD) and quantitation limits (LOQ) were also calculated. The proposed method was successfully applied for the determination of certain pharmaceutical dosage forms containing the studied drugs.

A simple, selective and sensitive luminescence method has been developed for the assay of etodolac (I), moxepril HCl (II) and fexofenadine HCl (III) in bulk drug and pharmaceutical formulations. The method is based on the luminescence sensitization of europium (Eu(3+)) by complexation with the studied drugs. The fluorescence intensities of the products were measured at 667 nm for (I) and at 615 for (II) and (III) while exciting at 276 for all the studied drugs. The fluorescence intensity was directly proportional to the concentration over the range (20-280), (40-240) and (30-80) ng/ml with limits of detection (LOD) = 0.93, 0.92 and 0.95 μg/ml for drugs I, II and III respectively. Optimum conditions for the formation of the complex in methanol were carefully studied. The proposed method was successfully applied for the assay of the studied drugs in pharmaceutical formulations with excellent recovery.

For several years, near-infrared spectroscopy (NIRS) has become an analytical technique of great interest for the pharmaceutical industry, particularly for the non-destructive analysis of dosage forms. The goal of this study is to show the capacity of this new technique to assay the active ingredient in low-dosage tablets. NIR spectroscopy is a rapid, non-destructive technique and does not need any sample preparation. A prediction model was built by using a partial least square regression fit method. The NIR assay was performed by transmission. The results obtained by NIR spectroscopy were compared with the conventional HPLC method for Montelukast tablets produced by Sigma pharmaceutical corp. The study showed that Montelukast tablets can be individually analyzed by NIR with high accuracy. It was shown that the variability of this new technique is less important than that of the conventional method which is the HPLC with UV detection.

The construction and performance characteristics of phenytoin sodium selective electrodes are detailed. Two types of electrodes: plastic membrane I and coated wire II, were constructed based on the incorporation of phenytoin sodium with tungstosilicic acid. The influence of membrane composition, kind of plasticizer, pH of the test solution, soaking time and the electrodes’ foreign ions were investigated. The electrodes showed a Nernstian response with a mean calibration graph slope of 30.9±0.1 and 28.9±0.1 mV decade−1 at 25°C for electrode I and II respectively, over a phenytoin sodium concentration range of 5×10−3−5×10−6 M and 1×10−3−1×10−6 M with a detection limit 1.3×10−6 M and 2.5×10−7 M for electrode I and II, respectively. The electrodes gave average selective precision and were usable within the pH range 6–10. Interference studies from common cations, alkaloids, sugars, amino acids and drug excipients are reported. The results obtained by the proposed electrodes were also applied successfully for the determination of the drug in pharmaceutical preparations and biological fluids.

Five Simple, accurate and rapid spectrophotometric and conductometric methods were developed for the determination of four third generation cephalosporins, namely, cefotaxime sodium (I) , cefoperazone sodium (II), ceftazidime pentahydrate (III) and cefdinir (IV) in pure active ingredient, pharmaceutical dosage forms and human urine. Method A: is based on the reaction of the sulphide ions produced from the alkaline hydrolysis of the cited four drugs with P- aminophenol (PAP). This reaction results in a thionine dye (phenothiazine derivative) formation which exhibits maximum absorbance at 545 nm. Method B: is based on oxidation of drug (I and III) with a known excess of n-bromosuccinimide (NBS) in acidic medium followed by the determination of unreacted amount of n-bromosuccinimide with metol and sulphanilic acid. The purple-red reaction product exhibits maximum absorbance at 520 nm. Method C: is based on the formation of yellow chelate between drug (IV) and palladium (II) chloride in buffered medium (pH 3.5) with an absorption maximum at 314 nm. Method D: is based on the reaction of drug (IV) with aqueous ninhydrin to give yellow colored product in the presence of bicarbonate with an absorption maximum at 433 nm . Method E: A conductometric method is based on the reaction of the four cited drugs with phosphotungstic acid (PTA) forming an ion associate in aqueous medium. Validation of the proposed methods was carried out. All proposed methods were successfully applied for the commercial dosage forms of the cited drugs. Method C was successfully applied for the determination of cefdinir in human urine.

Biological matrix effects are a source of significant errors in both electrospray (ESI) and atmospheric pressure chemical ionization (APCI) LC/MS. Glycerophosphocholines (GPChos) and 2-lyso-glycerophosphocholines (2-lyso GPChos) are known to fragment to form ions at m/z 184 and m/z 104, respectively. Phospholipids were used as markers to evaluate matrix effects resulting in both ion suppression and enhancement using ESI and APCI modes in the determination of chlorpheniramine in human plasma. Results revealed that GPChos and 2-lyso GPChos demonstrated very low ionization efficiency in the APCI mode, post-column infusion experiments were performed to confirm that suppression and enhancement matrix ionization effects coincided with the elution profiles of the phospholipids. The mean matrix effect for chlorpheniramine using APCI was 75% less than the mean matrix effect in ESI, making APCI the ionization method of choice initially even though the absolute response was lower than in the ESI mode. The resulting APCI method showed acceptable results according to the FDA guidelines; however, a multiple source relative matrix effects study demonstrated variability. It was concluded that an absolute matrix effects study in one source of biological fluid may be not sufficient to ensure the validity of the method in various sources of matrix. In order to obviate the multiple matrix source variability, we employed an isotopically labeled internal standard for quantification of chlorpheniramine in the ESI mode. An additional validation was completed with the use of chlorpheniramine-d(6) as the internal standard. This method met all acceptance criteria according to the FDA guidelines, and the relative matrix affects study was successful.

Phospholipids are known to cause matrix ionization effects during LC/MS/MS analysis of biological samples. Matrix effects involving endogenous phospholipids in the negative ESI mode have been investigated in this work for the determination of ibuprofen in human plasma. Glycerophosphocholines (GPChos) and 2-lysoglycerophosphocholines (2-lyso GPChos) were monitored as markers for endogenous matrix components. Various extraction solvents were evaluated to assess their abilities to remove phospholipids from plasma samples to minimize matrix effects. Post-column infusion experiments were applied to chromatographically resolve matrix effects that resulted from endogenous phospholipids. The resulting method was validated and linearity was obtained over a concentration range of 50 to 10,000 ng/mL.

This review article summarizes the opportunities for utilizing the green analytical chemistry (GAC) techniques and principles in the field of quality control (Q.C) of the pharmaceuticals. Green analytical chemistry is considered a branch of the green chemistry which is based on principles overlap with the sustained development ultimate goals. General definitions of quality and quality control, principles of Green Analytical Chemistry, proposals for greener sample pre-treatment, and greener chromatographic method of analysis to be applied in QC laboratories are herein discussed. The main goal is achieving more eco- friendly analysis in QC laboratories through different strategies and techniques replace the toxic reagents, and to modify or replace analytical methods and/or techniques with safer ones, making it possible to dramatically reduce the amounts of reagents consumed and waste generated. General definitions for quality and quality control: There are Several definitions of the term “quality”, yet one of them is of top importance to the perception of “Managing for Quality” concept. This definition describes product quality as “those features of products which meet customer needs and the freedom from deficiencies hereby provide customer satisfaction”. Managing for quality makes extensive use of three managerial processes: 1- Quality planning; 2- Quality control; 3- Quality improvement.

Matrix effects resulting in ion suppression or enhancement have been shown to be a source of variability and inaccuracy in bioanalytical mass spectrometry. Glycerophosphocholines may cause significant matrix ionization effects during quantitative LC/MS/MS analysis and are known to fragment to form characteristic ions (m/z 184) in electrospray mass spectrometry. This ion was used to monitor ion suppression effects in the determination of hydrocodone and pseudoephedrine in human plasma as a means to track and avoid these effects. The m/z 184 ion fragment was detected in both plasma extracts and solutions of phosphatidylcholine. Post-column infusion studies showed that the ion suppression for both drugs and internal standards correlated with the elution of phospholipids. HPLC conditions were adjusted to chromatographically resolve the peaks of interest from the phospholipids. Upon repeated injection, the elution time of the phospholipids decreased while elution of the analyte peaks remained unchanged. This resulted in co-elution and significantly affected peak shape and internal standard response for the analytes. It was decided to use the phospholipid fragment to monitor this matrix effect in validation samples. The resulting method demonstrated intra-day and inter-day precision within 4.5 and 5.6% for hydrocodone and pseudoephedrine, respectively, and accuracy within 8.9 and 8.7% for hydrocodone, and pseudoephedrine, respectively. There was no statistically significant difference in the internal standard response for the determination with and without monitoring the phospholipid fragment ion. We found that monitoring the phospholipid fragment was useful in method development to avoid the matrix effects, and in routine analysis to provide a practical way to ensure the avoidance of matrix effects in each individual sample.

A nalbuphine ion‐selective PVC membrane electrode based on ion‐pair complex of nalbuphine with tetra phenyl borate was prepared with di‐butyl sebacate as a plasticizer. The electrode exhibits a linear response with a Nernstain slope 59.6 mV decate−1 at 25°C with the concentration range of 1×10−6−1×10−2 M nalbuphine. The electrode response was not sensitive to pH changes from 3.5–7 and not affected by possible interfering species such as common inorganic cations, sugars and amino‐acids. The electrode shows good stability, reproducibility and fast response. These characteristics of the electrode enable it to be used successfully for the determination of nalbuphine hydrochloride in pure form and in pharmaceutical preparations.

A simple, rapid, sensitive and specific spectrophotometric method has been developed for the determination of two primary amines of pharmaceutical interest; dapsone and tranexamic acid. The method is based on condensation of the cited drugs with acetylacetone - formaldehyde mixture in acetic acid - sodium acetate buffer media by aid of heating at (97± 0.5°C) for a fixed time to yield a yellow colored condensation product ''dihydrolutidine derivative'' and possess a characteristic absorption maxima at 330 -345 nm. The variables affecting color development and the stability of the reaction product have been investigated and the conditions optimized. Beer's law is obeyed in the concentration range of 1 - 11 µg ml-1 with molar absorpitivities ranging from 1.475x104-2.015x104 L.mol-1cm-1 and Sandell sensitivities of 8.11x10-3-9.38x10-3 µg cm-2. The proposed spectrophotometric procedure was applied successfully for the determination of the cited drugs in some of their pharmaceutical formulations.

A simple, rapid, sensitive and accurate method for the determination of aciclovir, cefepime HCI, etamsylate and metoclopramide HCI in pure form and in pharmaceutical formulations is developed.The method is based on the fomabon of tris(o-phenanthroline) iron(ll) complex (Ferroin) upon the reaction of the ated drugs wrth iron(lll )-o- phenanthroline mixture. The ferroin complex is colorimetncally measured at λmax 510 nm against a reagent blank. 0ptimization of the experimental conditions is described. Beer's law is obeyed in the concentration range from 0.25–30 µg ml−1 with molar absorpitivities (ε) ranging from 4.796 x 103–9.51 2 x 104 L.mol−1.cm−1 and Sandell sensitivities (S) of 2.129 x 10−3–34.5 x 10−3 µg cm−2. The developed method is applied successfully for the determination of the cited drugs in pure forms and in the corresponding pharmaceutical formulations without any interferences from common excipients.

Two simple and accurate spectrophotometric methods for determination of timolol and enalapril maleate are described. The first method is based on chelate formation with palladium(II) chloride in buffered medium. The second method is based on the formation of the colored complex between palladium(II), eosin, and the two cited drugs using methylcellulose as surfactant to increase the solubility and intensity of the formed complexes. Under optimum conditions the complexes showed maximum absorption at 369.4 nm and 362.8 nm for timolol and enalapril maleate, respectively, in the first method and 552.2 and 550.6 nm for the second method. Apparent molar absorptivities were 1.8 x 10(3) and 1.3 x 10(3) and Sandell's sensitivities were 5.9 x 10(-4) and 2.7 x 10(-4) for timolol and enalapril maleate in the first method; in the second method molar absorptivities were 2.8 x 10(4) and 1.1 x 10(4) while Sandell's constants were 9.1 x 10(-3) and 2.3 x 10(-3) for timolol and enalapril maleate. The solutions of the complexes obeyed Beer's law in the concentration ranges 20-200 micro g mL(-1) and 50-300 micro g mL(-1) for timolol and enalapril maleate, respectively. In the second method, because the reaction was more sensitive the ranges were reduced to 1.6-16 micro g mL(-1) for timolol 8-56 micro g mL(-1) for enalapril maleate. The proposed methods were applied to the determination of the two drugs in their pharmaceutical formulation.

In this study, a simple, rapid, sensitive and green High Performance Thin Layer chromatography (HPTLC) method was developed and validated for determination of Simvastatin and Ezetimibe in tablet dosage form. The method was carried out in TLC silica gel of nano particle size on glass plate 60 F 254, 10 cm ×10 cm. Two solvent systems were chosen according to the Green Analytical Chemistry (GAC) parameters. Acetone: Heptane: Isopropyl alcohol in the proportion of 10:10:5, (v/v/v) with Rf Value for Simvastatin and Ezetimibe was 0.513 and 0.312 respectively. The linear regression coefficients were 0.999 and 0.998 for Simvastatin and Ezetimibe with respect to peak area and height in the concentration range of 600 - 1500 ng/spot and 150 - 375 ng/spot respectively. To get greener solvent, heptane was replaced with limonene in the second elution system but this system could separate either Simvastatin or Ezetimibe solely in single preparations but could not separate both of them simultaneously because both of them has almost the same Rf. The linear regression coefficients were 0.998 and 0.995 for Simvastatin and Ezetimibe respectively with the same concentration range of the first system. TLC plates of nano sized particles offer sharper separations due to small particle size and narrow fractionation. Theoretical plate heights (h values) are considerably smaller than those of the standard TLC plate. In addition diffusion and – as a consequence -band broadening are much lower. Also shorter developing times and shorter migration distances: After only a few centimeters an optimal separation has been achieved. Smaller samples of 0.01-0.1 μl (10-100 nanoliters). The samples applied are considerably smaller than with standard plates, thus it is possible to apply a large number of samples to a very small surface area, without samples interfering with each other. Finally increased detection sensitivity (nanogram level, hence nano plate). With fluorescence evaluation pico-gram quantities can be detected

The construction of a plasticised PVC matrix-type promazinium cation-selective membrane electrode and its use in the potentiometric determination of promazine hydrochloride in pharmaceutical preparations are described. It is based on the use of the ion-associate species, formed by promazinium cation and tetraphenylborate (TPB) counter ion. The basic electrode performance characteristics are evaluated according to IUPAC recommendations. It exhibited a linear response for 1 × 10−2−1 × 10−5 M of promazine hydrochloride solutions with a cationic Nernstian slope over the pH range 2–6. Common organic and inorganic cations showed negligible interference. Direct potentiometric determination of 1 × 10−2−1 × 10−5 M aqueous promazine hydrochloride using this membrane electrode system showed an average recovery of 99.5% with a mean standard deviation of 1.5%. This electrode was successfully used for monitoring the titration of promazine hydrochloride with sodium tetraphenyl borate and for determining promazine hydrochloride in ampoules.

Two colorimetric and titrimetric procedures are developed for determination of some cephalosporins, namely, cefotaxime sodium (CFT), cehroxime sodium (CFU) and ceftazidime pentahydrate (CFZ). The first method, a colorimetric method, was based on the reaction of these cited drugs with 4-chloro-7-nitrobenzofurazan (NBD-Cl), in the presence of 5x10-3 M borax, with the formation of stable colored chromogens with maximum absorbance in the range of 409 - 414 nm. All variables affecting the development of the colour have been investigated and the conditions were optimized. The method obeys Beer's law over concentration ranges of 19.09 - 95.49, 17.85 - 124.98 and 63.66 - 254.66 µg ml-1 of CFT, CFU and CFZ, respectively. Obedience to Beer's law permitted the successful application of the proposed method for the assay of cefuran, cefumax and fortum vials. The results obtained reveal good percentage recoveries, which are in good agreement with those obtained by the official methods. In the second method, the titrimetric method, the conditions for the oxidimetric titration of cephalosporins have been studied. The titration takes place because of catalytic quantities of KBr, which give rise to an intermediate that can be hydrolyzed to the sulfoxide. The operating conditions are described and a hypothesis is put forward concerning the mechanism of the reaction.

Two sensitive spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of certain cephalosporins (cefotaxime sodium and cefuroxime sodium). The spectrophotometric methods are based on the charge-transfer complex formation between these drugs as n-donors and 7,7,8,8-tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (p-CA) as pi-acceptors to give highly coloured complex species. The coloured products are measured spectrophotometrically at 838 and 529 nm for TCNQ and p-CA, respectively. Beer's law is obeyed in a concentration range of 7.6-15.2 and 7.1-20.0 microg x ml(-1) with TCNQ, 95.0-427.5 and 89.0-400.5 microg x ml-1 with p-CA for cefotaxime sodium and cefuroxime sodium, respectively. The atomic absorption spectrometric methods are based on the reaction of the above cited drugs after their alkali-hydrolysis with silver nitrate or lead acetate in neutral aqueous medium. The formed precipitates are quantitatively determined directly or indirectly through the silver or lead content of the precipitate formed or the residual unreacted metal in the filtrate by atomic absorption spectroscopy. The optimum conditions for hydrolysis and precipitation have been carefully studied. Beer's law is obeyed in a concentration range of 1.9-11.4 and 1.78-8.90 microg x ml(-1) with Ag(I), 14.2-57.0 and 13.3-53.4 microg x ml-1 with Pb(II) for cefotaxime sodium and cefuroxime sodium, respectively (for both direct and indirect procedures). The spectrophotometric and the atomic absorption spectrometric procedures hold well their accuracy and precision when applied to the analysis of cefotaxime sodium and cefuroxime sodium dosage forms.

The retention behaviour of some alkaloids, as test samples, on reversed-phase pre-coated thin layer chromatography in the presence of different ion-pair reagents was investigated. Trifluoroacetic acid (TFA), pentafluoropropionic acid (PFPA), and heptaflluorobutyric acid (HFBA) were used as counter ions. The dependence of R F values on the eluent composition, the chain length of the ion-pair reagent and the ratio of two ion-pair reagents in the eluent is described. The retention values of the tested alkaloids after impregnation of the plate with the counter ion, were investigated.

A simple, selective, and accurate high performance liquid chromatographic method for the determination of cephalexine, cefotaxime, and salbutamol sulphate was developed. The suggested method uses ODS column with methanol-phosphate buffer (pH 7) 6:4 as a mobile phase. The mean percentage recovery ranged from 97.4 to 98.8. The proposed method was applied to the determination of the selected drug in some pharmaceutical preparations. The statistical analysis of the results obtained was compared favourably with those given with the official method.

Simple methods are described for the determination of ethambutol in pharmaceutical preparations. They are based on the reaction of the drug with copper phosphate suspension in a borate buffer of pH 9.2, whereby a blue 1∶1 water-soluble copper-ethambutol complex is quantitatively formed. Four portions of the reaction solution are used for (i) measurement of copper by atomic-absorption spectrometry at 324.7 nm; (ii) potentiometric titration with EDTA with use of a solid-state copper ion-selective electrode; (iii) visual titration with EDTA (copper-PAN indicator); and (iv) spectrophotometric measurement of the copper-ethambutol complex at 640 nm. The results obtained are in good agreement and are better than those of the British Pharmacopoeia (BP) method.

A simple, sensitive and rapid liquid-liquid extraction method for the analysis of nicotinic acid (niacin) and its labeled internal standard nicotinic acid-d4 (niacin-d4) in human plasma was developed and validated. The analyte and its internal standard were isolated from acidified plasma using a single liquid-liquid extraction procedure with methyl-t-butyl ether. The extracted samples were analyzed by liquid chromatography-tandem mass spectrometry in positive electrospray ionization mode with multiple reaction monitoring. The calibration curves were linear in the measured range between 5 and 1000 ng/mL and the limit of detection was calculated as 122 pg/mL. The method required 250 microL of human plasma and the total run time between injections was 3.5 min. Matrix effects were assessed by post-column infusion experiments, phospholipids monitoring and post-extraction addition experiments. The extraction of phospholipids and niacin from plasma was studied under acidic, neutral and basic conditions. Acidic conditions were optimal for both the recovery of niacin and the removal of phospholipids; the degree of matrix effects for niacin was determined to be 2.5%. It was concluded that effective removal of matrix components can overcome low recovery issues associated with liquid-liquid extractions of polar analytes.

The construction and general performance characteristics of a novel potentiometric PVC membrane sensor based on pethidine-phosphomolybdate as electroactive material for the determination of pethidine are described. This sensor exhibits fast, stable and near-Nernstain response 55.24 +/- 0.1, over the concentration range 1.10(-2)-1.10(-5)M for pethidine-phosphomolybdate over pH 2-7. No interferences are caused by many organic, inorganic cations, alkaloids and amino acids. The sensor proved useful for determining pethidine in pure forms, pharmaceutical injections and monitoring the content uniformity assay of ampoules. The designed sensor also show good accuracy for the determination of pethidine in biological fluids.