Publications by authors named "Mohamed Korany"

29 Publications

  • Page 1 of 1

HPLC/Fluorescence-Diode Array Detection for Rapid and Reliable Determination of Illegal Synthetic Drugs in Male Sexual Herbal and Honey Remedies: Comparative Study with UFLC-MS.

J AOAC Int 2022 Mar 17. Epub 2022 Mar 17.

Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria, 21521 Egypt.

Background: Nutraceuticals, NTC, as honey and tablets with herbal extract are subjected to adulteration.

Objective: For NTCs claimed to enhance sexual performance, synthetic drugs (sildenafil, tadalafil, avanafil, vardenafil and dapoxetine) are common adulterants, so they were selected to be simultaneously analyzed in the current study. Natural aphrodisiacs (icariin and yohimbine) are claimed to be present in many fake NTCs, so they were also included in the study.

Methods: In order to achieve the target of the current study, three liquid chromatographic methods with different unique detectors were developed and validated.

Results: High performance liquid chromatography (HPLC) with fluorescence detection enables rapid and reliable determination of natively fluorescence yohimbine, tadalafil vardenafil and dapoxetine and it is the first report to analyze these compounds as adulterants in counterfeited NTC. Although diode array detector (DAD) enables the analysis of the seven adulterants, fluorescence detector (FLD) shows better sensitivity and selectivity with lower limits of quantitation and detection (LOQ and LOD). On the other hand, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) offers the advantages of peak identity confirmation, and it is of comparable sensitivity and the selectivity with HPLC-FD.

Conclusion: One or more of these synthetic drugs were found in the analyzed NTCs while natural aphrodisiacs were absent.

Highlights: Aphrodisiac nutraceuticals, NTCs, were analyzed for adulterants; Five aphrodisiac synthetic drugs (adulterants) were analyzed; two natural claimed aphrodisiac were analyzed in these NTCs; UFLC-MS, HPLC-DAD/FLD were compared for illicit NTCs analysis; all NTCs show synthetic aphrodisiac presence with absence of natural ones.
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http://dx.doi.org/10.1093/jaoacint/qsac037DOI Listing
March 2022

Stability-indicating RP-HPLC assay of three novel oral anticoagulants binary mixtures with rosuvastatin calcium: Application to pharmaceutical preparations and human plasma.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Feb 15;1193:123160. Epub 2022 Feb 15.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt; Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

The binary mixtures of the novel oral anticoagulants (NOACs); Apixaban (APX), Edoxaban tosylate (EDX) and Rivaroxaban (RIV) with the lipid lowering statin; Rosuvastatin calcium were analyzed using a validated HPLC-DAD method. This method was suitable for the quantitative assay of the targeted mixtures in tablets and human plasma. The analysis in dosage form was a stability indicating one where the drugs were separated from possible degradation products arising from applying different stress conditions. For analysis in human plasma, EDX was used as internal standard in APX/ROS and RIV/ROS mixtures, while APX was used as internal standard in EDX/ROS mixture and the method was validated according to FDA regulation for analysis in biological fluids. A ZORBAX Eclipse column C18 (4.6 × 150 mm × 5 µm) was used as stationary phase with a gradient eluting mobile phase composed of acidified water and acetonitrile. The method selectivity was demonstrated by its ability to simultaneously analyze the drugs in presence of possible forced degradation products and dosage form excipients and in presence of plasma interferences (analysis in biological fluid) at a single wavelength (291 nm) with the use of the internal standard. The simplicity of the method emphasizes its capability to analyze the drugs in pharmaceutical preparations and human plasma. This is very important in regular clinical monitoring of the drugs plasma concentrations for cardiovascular patients medicated with either of these combinations, as prophylaxis from stroke, in order to prevent severe bleeding and to achieve optimum dose adjustment.
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http://dx.doi.org/10.1016/j.jchromb.2022.123160DOI Listing
February 2022

HPLC with fluorescence detection for the bioanalysis and pharmacokinetic study of Doxorubicin and Prodigiosin loaded on eco-friendly casein nanomicelles in rat plasma.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Dec 15;1187:123043. Epub 2021 Nov 15.

Department of Chemistry of Natural and Microbial Products, National Research Centre, Dokki, Giza, 12622, Egypt. Electronic address:

A rapid, efficient, and sensitive liquid chromatographic assay hyphenated to fluorometric detector (HPLC-FLD) was developed and validated for the determination of doxorubicin (DXR) and prodigiosin (PDG) in rat plasma. The sample pre-treatment involves a protein precipitation with acetonitrile with satisfying extraction efficiency (98% and 85% for DXR and PDG, respectively). The chromatographic separation was accomplished using stationary phase: Agilent Zorbax Eclipse plus-C18 analytical column (250 × 4.6 mm, 5 μm) and gradient eluting mobile phase of ammonium acetate (pH = 3), acetonitrile and methanol with programmed fluorescence detection. As the proposed method has been validated, it was subsequently implemented to evaluate DXR and PDG loaded on novel eco-friendly Casein nano drug delivery system after intravenous injection in healthy rats. A comparative pharmacokinetics' study was carried out in rats for DXR in free form, DXR alone entrapped in the nanomicelle and DXR with PDG entrapped in the nano micelle. After testing the differences in pharmacokinetic parameters of the different formulations using ANOVA, the results showed insignificant differences among the tested parameters. This indicates that the presented nanomicelle delivery system has succeeded to incorporate PDG and DXR in a hydrophilic, safe, and potent formulation. This novel nanomicelle has negligible effect on the distribution and elimination of DXR.
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http://dx.doi.org/10.1016/j.jchromb.2021.123043DOI Listing
December 2021

A Review on Analytical Strategies for the Assessment of Recently Approved Direct Acting Antiviral Drugs.

Crit Rev Anal Chem 2021 Jun 17:1-23. Epub 2021 Jun 17.

Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria, Egypt.

Human beings are in dire need of developing an efficient treatment against fierce viruses like hepatitis C virus (HCV) and Coronavirus (COVID-19). These viruses have already caused the death of over two million people all over the world. Therefore, over the last years, many direct-acting antiviral drugs (DAADs) were developed targeting nonstructural proteins of these two viruses. Among these DAADs, several drugs were found more effective and safer than the others as sofosbuvir, ledipasvir, grazoprevir, glecaprevir, voxilaprevir, velpatasvir, elbasvir, pibrentasvir and remdesivir. The last one is indicated for COVID-19, while the rest are indicated for HCV treatment. Due to the valuable impact of these DAADs, larger number of analytical methods were required to meet the needs of the clinical studies. Therefore, this review will highlight the current approaches, published in the period between 2017 to present, dealing with the determination of these drugs in two different matrices: pharmaceuticals and biological fluids with the challenges of analyzing these drugs either alone, with other drugs, in presence of interferences (pharmaceutical excipients or endogenous plasma components) or in presence of matrix impurities, degradation products and metabolites. These approaches include spectroscopic, chromatographic, capillary electrophoretic, voltametric and nuclear magnetic resonance methods that have been reported during this period. Moreover, the analytical instrumentation and methods used in determination of these DAADs will be illustrated in tabulated forms.
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http://dx.doi.org/10.1080/10408347.2021.1923456DOI Listing
June 2021

A Validated Stability-Indicating HPTLC Assay for Determination of 10-Hydroxy-2-Decenoic Acid Content in Royal Jelly Products Using Robust Regression Methods.

J Chromatogr Sci 2020 Jun;58(6):520-534

Department of Pharmacognosy, Faculty of Pharmacy, University of Alexandria, El-Khartoum square - Azarita, Alexandria 21521, Egypt.

A new, simple, stability-indicating high-performance thin-layer chromatography method was developed for the quantification of 10-hydroxy-2-decenoic acid (10-HDA) in some royal jelly products marketed in Egypt. The used solvent system was chloroform:acetic acid (10:1, v/v) and the bands were measured densitometrically at 210 nm. First- and second-derivative treatments of the data were performed. The present study shows a comparison between three statistical regression methods for handling data: parametric, nonparametric and weighted regression (WR) methods. The developed methods were validated as per International Conference on Harmonization guidelines. To validate the stability-indicating power of the developed analytical method, the royal jelly standard was subjected to forced degradation studies including the effect of hydrolysis, oxidation, photolysis and dry heat. It was found that derivative treatment of the chromatographic response data gives improved quantitation and sensitivity of the chromatographic signals. Weighted regression of the response data is found to be advantageous over the use of both parametric and nonparametric regression models. This was shown by a great enhancement in the accuracy and precision in the analysis of 10-HDA in royal jelly products. The % recovery in case of WR was 99.92 ± 0.16, while % recovery in case of nonparametric and parametric regressions were 99.56 ± 0.25 and 98.63 ± 0.65, respectively.
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http://dx.doi.org/10.1093/chromsci/bmaa016DOI Listing
June 2020

Exhibiting the diagnostic face of selenium nanoparticles as a radio-platform for tumor imaging.

Bioorg Chem 2020 07 5;100:103910. Epub 2020 May 5.

Radioactive Isotopes and Generators Department, Hot Labs Center, Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt. Electronic address:

Selenium nanoparticles (SeNPs) have become one of the most prospective and promising tools in the course of cancer diagnosis and therapy. Here we describe the synthesis of a novel radioactive platform for tumor imaging using selenium nanoparticles. SeNPs were synthetized using dithionite and glutathione as reducing and capping agent respectively with 5 mmol/L sodium selenite as a precursor and then SeNPs radiolabeled with technetium-99 m, the most common and famous radioactive isotope used for imaging purposes. A characteristic profile for the synthesized SeNPs was performed including size analysis, zeta potential, antioxidant activity, radiochemical yield and in-vivo biodistribution in normal and solid tumor bearing mice. Size analysis showed amorphous SeNP cores of a mean diameter of 21 ± 5 nm with a hydrodynamic size of 43 ± 8 nm and -28 mV zeta potential. The particles also showed a superior antioxidant activity of radical scavenging activity 55.6% according to DPPH assay, in addition, satisfying radiochemical yield up to 97 ± 1.5 was achieved. In vivo studies were applied on male Swiss albino mice that demonstrated a good biodistribution pattern in normal mice with a moderate accumulation in liver at 30 min post injection. Excellent T/NT ratios were obtained in solid tumor bearing mice throughout the experimental time points. The as-synthetized selenium nanoparticles demonstrated surprising and satisfying features which make them promising enough for tumor theranosis.
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http://dx.doi.org/10.1016/j.bioorg.2020.103910DOI Listing
July 2020

Analysis of astragalosides I, II and IV in some Egyptian Astragalus species and Astragalus dietary supplements using high-performance liquid chromatography/evaporative light scattering detector and non-parametric regression.

Phytochem Anal 2020 Sep 5;31(5):594-605. Epub 2020 Feb 5.

Department of Pharmacognosy, Faculty of Pharmacy, University of Alexandria, Alexandria, 21521, Egypt.

Introduction: GenuTs Astragalus L. is characterised by the presence of cycloartane saponins which have wide biological activities such as antioxidant, immunomodulating' hepatoprotective and anti-inflammatory activities. From these cycloartane saponins are astragalosides I, II and IV which have been regarded as the most important active constituents in Astragalus species.

Objectives: This work describes the quantitative analysis of astragalosides I, II and IV in some Egyptian Astragalus species and Astragalus dietary supplements in a single run by high-performance liquid chromatography/evaporative light scattering detector (HPLC/ELSD) using gradient elution.

Methodology: The method of quantitation adopted in this study is the standard addition method. First and second derivative treatment of the data was performed, and the study presents comparison between two statistical regression methods for handling data; parametric and non-parametric regression methods.

Results: Derivative treatment of the chromatographic response data gives improved quantitation of the chromatographic signals. Non-parametric regression of the data using Theil's method is advantageous over the usual least squares method as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points.

Conclusion: Due to the simplicity and the good accuracy and reproducibility of the suggested methods, they could be used for analysis and quality control of Astragalus species and Astragalus dietary supplements.
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http://dx.doi.org/10.1002/pca.2925DOI Listing
September 2020

Potentiometric sensor based on novel flowered-like Mg-Al layered double hydroxides/multiwalled carbon nanotubes nanocomposite for bambuterol hydrochloride determination.

Mater Sci Eng C Mater Biol Appl 2019 Jul 28;100:186-195. Epub 2019 Feb 28.

Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.

Nowadays, development of highly efficient potentiometric sensors attracts the attention of many researchers over the world; due to the great expansion of portable analytical devices. This study aims to apply a current development to the construction and sense of carbon paste sensors based on flowered-like Mg-Al layered double hydroxides/multiwalled carbon nanotubes (FLLDH/MWCNTs) (sensor І), FLLDH/titanate nanotubes (TNTs) (sensor ІІ) and MWCNTs/TNTs (sensor ІІІ) nanocomposites for bambuterol hydrochloride analysis; to enhance the potentiometric response towards determination of the drug. The sensors exhibited excellent Nernstian slopes 58.8 ± 0.5, 58.5 ± 0.8 and 57.4 ± 0.7 mV/decade with linear working ranges of 1.0 × 10-1.0 × 10, 1.0 × 10-1.0 × 10 and 1.0 × 10-1.0 × 10 mol L, detection limits 2.3 × 10, 2.5 × 10and 7.5 × 10 mol L and quantification limits of 7.6 × 10, 8.3 × 10and 2.5 × 10 mol L for sensor І, ІІ and ІІІ, respectively. The selectivity behaviour of the investigated sensors was tested against biologically important blood electrolytes (Na, K, Mg, Ca). The proposed analytical method was successfully applied for BAM determination in pure drug, pharmaceutical products, surface water, human plasma and urine samples with excellent recovery data (99.62, 99.10 and 98.95%) for the three sensors, respectively.
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http://dx.doi.org/10.1016/j.msec.2019.02.103DOI Listing
July 2019

Voltammetric analysis of dantrolene and its active metabolite with indomethacin in rat plasma.

Bioanalysis 2019 Jan 12;11(2):73-84. Epub 2018 Dec 12.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, El-Messalah, Alexandria 21521, Egypt.

Aim: Differential pulse polarography was used for the concurrent analysis of the coadministered dantrolene (DAN) and indomethacin (IND) in plasma.

Materials & Methods: DAN and IND, Hanging mercury drop electrode and Britton-Robinson buffer at pH 5 were used. In plasma, cathodic reduction of DAN nitro group and its active metabolite at -0.2 V was done. IND was analyzed after carbonyl group reduction at -1.1 V.

Results: Drugs determination in rat plasma with good recoveries and low limit of quantitation was done. Application to trace analysis of drugs in rat plasma was done with C and T determination.

Conclusion: This technique shows high sensitivity, simplicity and low cost. The method is US FDA validated and it is applicable to human level.
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http://dx.doi.org/10.4155/bio-2018-0165DOI Listing
January 2019

Chemometrics-assisted spectrophotometric green method for correcting interferences in biowaiver studies: Application to assay and dissolution profiling study of donepezil hydrochloride tablets.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Jun 27;199:328-339. Epub 2018 Mar 27.

SPIMACO MISR for Pharmaceutical Industries, Borg El-Arab, Alexandria, Egypt.

A green, simple and cost effective chemometric UV-Vis spectrophotometric method has been developed and validated for correcting interferences that arise during conducting biowaiver studies. Chemometric manipulation has been done for enhancing the results of direct absorbance, resulting from very low concentrations (high incidence of background noise interference) of earlier points in the dissolution timing in case of dissolution profile using first and second derivative (D1 & D2) methods and their corresponding Fourier function convoluted methods (D1/FF& D2/FF). The method applied for biowaiver study of Donepezil Hydrochloride (DH) as a representative model was done by comparing two different dosage forms containing 5mg DH per tablet as an application of a developed chemometric method for correcting interferences as well as for the assay and dissolution testing in its tablet dosage form. The results showed that first derivative technique can be used for enhancement of the data in case of low concentration range of DH (1-8μgmL) in the three different pH dissolution media which were used to estimate the low drug concentrations dissolved at the early points in the biowaiver study. Furthermore, the results showed similarity in phosphate buffer pH6.8 and dissimilarity in the other 2pH media. The method was validated according to ICH guidelines and USP monograph for both assays (HCl of pH1.2) and dissolution study in 3pH media (HCl of pH1.2, acetate buffer of pH4.5 and phosphate buffer of pH6.8). Finally, the assessment of the method greenness was done using two different assessment techniques: National Environmental Method Index label and Eco scale methods. Both techniques ascertained the greenness of the proposed method.
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http://dx.doi.org/10.1016/j.saa.2018.03.059DOI Listing
June 2018

High performance thin-layer and high performance liquid chromatography coupled with photodiode array and fluorescence detectors for analysis of valsartan and sacubitril in their supramolecular complex with quantitation of sacubitril-related substance in raw material and tablets.

J Chromatogr Sci 2018 Jul;56(6):498-509

Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria, Egypt.

Valsartan (VAL) and sacubitril (SAC) are combined in a supramolecular complex, LCZ696, which is a newly approved remedy for heart failure. SAC-related substance (biphenyl methyl pyrrolidinone [BMP]) which also appears as an intermediate during SAC synthesis is considered to be a suspected impurity for SAC and/or LCZ696 tablets. The study investigates the analysis of VAL and SAC in their supramolecular complex along with SAC-related substance, BMP, using high performance thin-layer chromatography (HPTLC) and high performance liquid chromatography (HPLC) with two different detectors; fluorescence detector (FLD) and diode array detector (DAD). The work aimed at analyzing BMP at low levels in the presence of its parent drug, SAC. BMP was successfully analyzed at a level of 0.167, 1 and 3% of its parent drug, SAC upon using HPLC-FLD, HPLC-DAD and HPTLC, respectively. For HPLC-FLD, the detector was set at λex/λem (nm/nm): 0-4.5 min at 255/374; 4.5-6 min at 255/314, for achieving an adequate sensitivity of the method to monitor and quantify VAL and SAC in the presence of BMP. Low limits of detection (8.3, 3.3 and 1.7 ng mL-1) and limits of quantitation (25, 10 and 5 ng mL-1) values obtained for VAL, SAC and BMP, respectively, upon using FLD suggest that low level of baseline noise enables the detection and quantitation of low BMP concentration.
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http://dx.doi.org/10.1093/chromsci/bmy021DOI Listing
July 2018

Least median of squares and iteratively re-weighted least squares as robust linear regression methods for fluorimetric determination of α-lipoic acid in capsules in ideal and non-ideal cases of linearity.

Luminescence 2018 Jun 26;33(4):742-750. Epub 2018 Mar 26.

Department of Analytical and Pharmaceutical Chemistry, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt.

This study outlines two robust regression approaches, namely least median of squares (LMS) and iteratively re-weighted least squares (IRLS) to investigate their application in instrument analysis of nutraceuticals (that is, fluorescence quenching of merbromin reagent upon lipoic acid addition). These robust regression methods were used to calculate calibration data from the fluorescence quenching reaction (∆F and F-ratio) under ideal or non-ideal linearity conditions. For each condition, data were treated using three regression fittings: Ordinary Least Squares (OLS), LMS and IRLS. Assessment of linearity, limits of detection (LOD) and quantitation (LOQ), accuracy and precision were carefully studied for each condition. LMS and IRLS regression line fittings showed significant improvement in correlation coefficients and all regression parameters for both methods and both conditions. In the ideal linearity condition, the intercept and slope changed insignificantly, but a dramatic change was observed for the non-ideal condition and linearity intercept. Under both linearity conditions, LOD and LOQ values after the robust regression line fitting of data were lower than those obtained before data treatment. The results obtained after statistical treatment indicated that the linearity ranges for drug determination could be expanded to lower limits of quantitation by enhancing the regression equation parameters after data treatment. Analysis results for lipoic acid in capsules, using both fluorimetric methods, treated by parametric OLS and after treatment by robust LMS and IRLS were compared for both linearity conditions.
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http://dx.doi.org/10.1002/bio.3471DOI Listing
June 2018

Green gas chromatographic stability-indicating method for the determination of Lacosamide in tablets. Application to in-vivo human urine profiling.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Apr 7;1083:75-85. Epub 2018 Mar 7.

SPIMACO MISR for Pharmaceutical Industries, Borg El-Arab, Alexandria, Egypt.

A direct, eco-friendly, stability-indicating GC method was developed for the determination of Lacosamide (LCM) in tablet dosage forms in presence of its degradation products as well as in human urine in presence of the co-administered drug Zonisamide (ZON). The assay method in tablets was validated according to the ICH guidelines, while the method for determination of LCM in urine was validated according to FDA; Bioanalytical Method Validation guidance. Linear response (r = 0.9998) was observed over the range of 20-280 μg/mL of LCM, with detection and quantitation limits of 5.871 and 19.57 μg/mL, respectively for the tablet assay method. While (r = 0.9999) was observed over the range of 0.5-20 μg/mL of LCM, with detection and quantitation limits of 67 and 233 ng mL, respectively for the urine analysis method. Under various stress conditions, the investigation of LCM forced degradation behaviour was carried out. Furthermore, monitoring of the drug in urine followed by construction of its urine profile was done after the administration of 50 mg tablet of LCM to three healthy volunteers so as to prove the ability of the method to be applied in assaying LCM in human urine. The method showed also successful separation of LCM and the co-administered drug ZON in urine. Finally, the greenness of the method was assessed using National Environmental Methods Index label and Eco scale methods.
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http://dx.doi.org/10.1016/j.jchromb.2018.02.033DOI Listing
April 2018

Spur-of-the-Moment Modification in National Treatment Policies Leads to a Surprising HCV Viral Suppression in All Treated Patients: Real-Life Egyptian Experience.

J Interferon Cytokine Res 2018 02 22;38(2):81-85. Epub 2018 Jan 22.

2 Endemic Medicine and Hepato-Gastroenterology Department, Faculty of Medicine, Cairo University , Cairo, Egypt .

The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming. All group 1 patients (1,214 patients) achieved SVR12 (100%) and this was statistically significant when compared with the overall SVR12 in group 2 [8,869 patients with sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse events were reported in both groups. In this real-life treatment experience, interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV viral suppression in all treated patients.
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http://dx.doi.org/10.1089/jir.2017.0121DOI Listing
February 2018

Analysis of Closely Related Antioxidant Nutraceuticals Using the Green Analytical Methodology of ANN and Smart Spectrophotometric Methods.

J AOAC Int 2017 Jan;100(1):8-17

Pharos University in Alexandria, Faculty of Pharmacy and Drug Manufacturing, Department of Analytical and Pharmaceutical Chemistry, Alexandria, Egypt.

Two new, simple, and specific green analytical methods are proposed: zero-crossing first-derivative and chemometric-based spectrophotometric artificial neural network (ANN). The proposed methods were used for the simultaneous estimation of two closely related antioxidant nutraceuticals, coenzyme Q10 (Q10) and vitamin E, in their mixtures and pharmaceutical preparations. The first method is based on the handling of spectrophotometric data with the first-derivative technique, in which both nutraceuticals were determined in ethanol, each at the zero crossing of the other. The amplitudes of the first-derivative spectra for Q10 and vitamin E were recorded at 285 and 235 nm respectively, and correlated with their concentrations. The linearity ranges of Q10 and vitamin E were 10-60 and 5.6-70 μg⋅mL-1, respectively. The second method, ANN, is a multivariate calibration method and it was developed and applied for the simultaneous determination of both analytes. A training set of 90 different synthetic mixtures containing Q10 and vitamin E in the ranges of 0-100 and 0-556 μg⋅mL-1, respectively, was prepared in ethanol. The absorption spectra of the training set were recorded in the spectral region of 230-300 nm. By relating the concentration sets (x-block) with their corresponding absorption data (y-block), gradient-descent back-propagation ANN calibration could be computed. To validate the proposed network, a set of 45 synthetic mixtures of the two drugs was used. Both proposed methods were successfully applied for the assay of Q10 and vitamin E in their laboratory-prepared mixtures and in their pharmaceutical tablets with excellent recovery. These methods offer advantages over other methods because of low-cost equipment, time-saving measures, and environmentally friendly materials. In addition, no chemical separation prior to analysis was needed. The ANN method was superior to the derivative technique because ANN can determine both drugs under nonlinear experimental conditions. Consequently, ANN would be the method of choice in the routine analysis of Q10 and vitamin E tablets. No interference from common pharmaceutical additives was observed. Student's t-test and the F-test were used to compare the two methods. No significant difference was recorded.
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http://dx.doi.org/10.5740/jaoacint.16-0203DOI Listing
January 2017

First derivative emission spectrofluorimetric method for the determination of LCZ696, a newly approved FDA supramolecular complex of valsartan and sacubitril in tablets.

Luminescence 2017 Dec 1;32(8):1417-1425. Epub 2017 Jun 1.

Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria, Egypt.

LCZ696 (sacubitril/valsartan, Entresto™) is a therapy lately approved by United States Food and Drug Administration (US FDA) as a heart failure therapy. It is claimed to decrease the mortality rate and hospitalization for patients with chronic heart failure. This study is considered as the first report to investigate the fluorimetric behavior of sacubitril in addition to pursuing all the different conditions that may affect its fluorescence. Various conditions were studied, for example studying the effects of organized media, solvents and pH, which may affect the fluorescence behavior of sacubitril. For the simultaneous determination of the newly approved supramolecular complex of valsartan (VAL) and sacubitril (SAC) in their tablets, a sensitive and simple first derivative spectrofluorimetric method was developed. The method involved the measurement of native fluorescence at 416 nm and 314 nm (λ 249 nm) for VAL and SAC, respectively. The first (D1) derivative technique was applied to the emission data to resolve a partial overlap that appeared in their emission spectra. The proposed method was successfully applied for the assay of the two drugs in their supramolecular complex LCZ696 with no interference from common pharmaceutical additives. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines were followed in order to validate the proposed method.
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http://dx.doi.org/10.1002/bio.3339DOI Listing
December 2017

Real life Egyptian experience of efficacy and safety of Simeprevir/Sofosbuvir therapy in 6211 chronic HCV genotype IV infected patients.

Liver Int 2017 04 4;37(4):534-541. Epub 2016 Nov 4.

Hepatology & Endemic Medicine Department, Cairo University, Cairo, Egypt.

Background & Aims: Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy.

Methods: This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy.

Results: Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%).

Conclusion: Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.
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http://dx.doi.org/10.1111/liv.13266DOI Listing
April 2017

Mass Spectrometric and Computational Investigation of the Protonated Carnosine-Carboplatin Complex Fragmentation.

Inorg Chem 2015 Aug 4;54(16):7885-97. Epub 2015 Aug 4.

†Dipartimento di Chimica e Tecnologie Chmiche, Università della Calabria, I-87036 Arcavacata di Rende, Italy.

Platinum(II)-based anticancer drugs are square-planar d(8) complexes that, activated by hydrolysis, cause cancer cell death by binding to nuclear DNA and distorting its structure. For that reason, interactions of platinum anticancer drugs with DNA have been extensively investigated, aiming at disentangling the mechanism of action and toxicity. Less attention, however, has been devoted to the formation of adducts between platinum drugs with biological ligands other than DNA. These adducts can cause the loss and deactivation of the drug before it arrives at the ultimate target and are also thought to contribute to the drug's toxicity. Here are reported the outcomes of electrospray ionization mass spectrometry experiments and density functional theory (DFT) computations carried out to investigate the fragmentation pathways of the protonated carnosine-carboplatin complex, [Carnosine + CarbPt + H](+). DFT calculations at the B3LYP/LANL2DZ level employed to probe fragmentation mechanisms account for all experimental data. Because of the relative rigidity of the structure of the most stable 1A conformer, stabilized by three strong hydrogen bonds, the first step of all of the examined fragmentation pathways is the interconversion of the 1A conformer into the less stable structure 1B. Formation of the [Carnosine + H](+) fragment from the precursor ion, [Carnosine + CarbPt + H](+), is calculated to be the lowest-energy process. At slightly higher energies, the loss of two amino groups is observed to produce the [Carnosine + (CarbPt - NH3) + H](+) and [Carnosine + (CarbPt - 2NH3) + H](+) ions. At significantly higher energies, the loss of CO2 occurs, yielding the final [Carnosine + (CarbPt - NH3) - CO2 + H](+) and [Carnosine + (CarbPt - 2NH3) - CO2 + H](+) products. Formation of the [CarbPt + H](+) fragment from [Carnosine + CarbPt + H](+), even if not hampered by a high activation barrier, is calculated to be very unfavorable from a thermodynamic point of view.
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http://dx.doi.org/10.1021/acs.inorgchem.5b00959DOI Listing
August 2015

Application of derivative spectrophotometry under orthogonal polynomial at unequal intervals: determination of metronidazole and nystatin in their pharmaceutical mixture.

Spectrochim Acta A Mol Biomol Spectrosc 2015 May 7;143:281-7. Epub 2015 Feb 7.

Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, University of Alexandria, Egypt.

This paper discusses a general method for the use of orthogonal polynomials for unequal intervals (OPUI) to eliminate interferences in two-component spectrophotometric analysis. In this paper, a new approach was developed by using first derivative D1 curve instead of absorbance curve to be convoluted using OPUI method for the determination of metronidazole (MTR) and nystatin (NYS) in their mixture. After applying derivative treatment of the absorption data many maxima and minima points appeared giving characteristic shape for each drug allowing the selection of different number of points for the OPUI method for each drug. This allows the specific and selective determination of each drug in presence of the other and in presence of any matrix interference. The method is particularly useful when the two absorption spectra have considerable overlap. The results obtained are encouraging and suggest that the method can be widely applied to similar problems.
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http://dx.doi.org/10.1016/j.saa.2015.01.076DOI Listing
May 2015

Development and optimization of a capillary zone electrophoresis technique for simultaneous determination of miconazole nitrate and hydrocortisone acetate in a cream pharmaceutical formulation.

J AOAC Int 2013 Nov-Dec;96(6):1295-301

A simple, fast, inexpensive, and reliable capillary zone electrophoresis (CZE) method for the determination of a mixture of miconazole nitrate (MCZ) and hydrocortisone acetate (HCZ) in a cream formulation has been developed and validated. Optimum conditions were sodium dihydrogen phosphate buffer (50 mM, pH 4) and 30 kV applied voltage in a 85 cm x 75 pm id capillary. Direct UV detection at 230 nm led to adequate sensitivity without interference from the sample excipients. MCZ and HCZ migrated in approximately 165 and 415 s, respectively. The analytical curves had a coefficient of correlation, r, of 0.9999 and 0.9996 for MCZ and HCZ, respectively. The LOD and LOQ were 0.28 and 0.93 microg/mL for MCZ and 0.38 and 1.27 microg/mL for HCZ, respectively. Thus, excellent accuracy and precision were obtained. Recoveries varied from 98 to 102%, and intraday and interday precision, calculated as the RSD, were less than 2.0% for each drug. The proposed CZE method displayed advantageous performance characteristics and can be considered suitable for QC of the MCZ and HCZ cream formulation.
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http://dx.doi.org/10.5740/jaoacint.11-343DOI Listing
April 2014

Liquid chromatographic determination of amikacin sulphate after pre-column derivatization.

J Chromatogr Sci 2014 Sep 4;52(8):837-47. Epub 2013 Sep 4.

Pharco-B International Company for Pharmaceuticals, Borg El-Arab, Alexandria, Egypt.

A novel high performance liquid chromatographic (HPLC) method with a pre-column derivatization reaction has been developed and validated. The method was used for the determination of the aminoglycoside antibiotic amikacin sulphate (AMK) in the presence of its synthetic precursor kanamycin sulphate in pure form and in different pharmaceutical preparations. The pre-column derivatization was based on Hantzsch condensation reaction and the obtained coloured products were separated using an isocratic reversed-phase high performance liquid chromatographic method. The separation was achieved on a Spherisorb C18 ODS2 (250 × 4.6 mm, 5 μm) column using a mobile phase composed of acetonitrile-0.1 M sodium acetate buffer (pH 5.0; 25:75, v/v). The column temperature was adjusted at 35 °C and the flow rate at 2 mL min(-1). The detection was carried out at 330 nm by using photo-diode array detector. Different conditions for the optimization of the derivatization reaction as well as for the HPLC measurement were studied. Moreover, AMK was subjected to forced degradation by oxidation, hydrolysis, photolysis and dry heat. Degradation products did not interfere with the assay, which can thus be considered selective and specific. The proposed method was validated for linearity, precision, accuracy, specificity and robustness. Also, it was used to check the purity of AMK in the presence of KAN (related impurity) at the pharmacopoeial limit (0.5%).
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http://dx.doi.org/10.1093/chromsci/bmt126DOI Listing
September 2014

Development and validation of spectrophotometric and HPTLC methods for simultaneous determination of rosiglitazone maleate and metformin hydrochloride in the presence of interfering matrix excipients.

Drug Dev Ind Pharm 2014 Sep 8;40(9):1190-8. Epub 2013 Jul 8.

Faculty of Pharmacy, Department of Pharmaceutical Chemistry, King Abdulaziz University , Jeddah , Saudi Arabia .

Two simple methods have been developed and validated for the simultaneous determination of rosiglitazone maleate (ROS) and metformin hydrochloride (MET) in synthetic mixtures and coated tablets in a ratio of 1:250 (ROS:MET). The first method was a spectrophotometric one. The minor component, ROS was determined by measuring the values of absorbance at λmax 312 nm and the D1 amplitudes at 331 nm where MET shows no absorption contribution. However, absorbance interferences from tablet excipients were successfully corrected by D1 at 331 nm zero-crossing technique. Study of spectral interference from tablet excipients was included in the text. Standard curves for Amax and D1 methods were in the concentration range 20.0-80.0 μg mL(-1). The major component, MET was determined both in binary mixtures and tablets by measuring its Amax at 236 nm. Extensive dilution eliminated any absorption contribution from the coexisting ROS or tablet matrix. Standard curves showed linearity in the concentration range 4.0-12.8 μg mL(-1). The second method was based on high performance thin layer chromatography (HPTLC) separation of the two drugs followed by densitometric measurements of their spots at 230 nm. The separation was carried out on Merck HPTLC aluminium sheets of silica gel 60 F254 using methanol:water:NH4Cl 1% w/v (5:4:1 v/v/v) as the mobile phase. Linear calibration graphs of peak area values were obtained versus concentrations in the range of 0.4-2.0 μg band(-1) and 20.0-100.0 μg band(-1) for ROS and MET, respectively. According to International Conference on Harmonisation (ICH) guidelines, different validation parameters were verified for the two methods and presented.
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http://dx.doi.org/10.3109/03639045.2013.810634DOI Listing
September 2014

Comparative study of some robust statistical methods: weighted, parametric, and nonparametric linear regression of HPLC convoluted peak responses using internal standard method in drug bioavailability studies.

Anal Bioanal Chem 2013 May 10;405(14):4835-48. Epub 2013 Mar 10.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, El-Messalah, Alexandria, Egypt.

This manuscript discusses the application and the comparison between three statistical regression methods for handling data: parametric, nonparametric, and weighted regression (WR). These data were obtained from different chemometric methods applied to the high-performance liquid chromatography response data using the internal standard method. This was performed on a model drug Acyclovir which was analyzed in human plasma with the use of ganciclovir as internal standard. In vivo study was also performed. Derivative treatment of chromatographic response ratio data was followed by convolution of the resulting derivative curves using 8-points sin x i polynomials (discrete Fourier functions). This work studies and also compares the application of WR method and Theil's method, a nonparametric regression (NPR) method with the least squares parametric regression (LSPR) method, which is considered the de facto standard method used for regression. When the assumption of homoscedasticity is not met for analytical data, a simple and effective way to counteract the great influence of the high concentrations on the fitted regression line is to use WR method. WR was found to be superior to the method of LSPR as the former assumes that the y-direction error in the calibration curve will increase as x increases. Theil's NPR method was also found to be superior to the method of LSPR as the former assumes that errors could occur in both x- and y-directions and that might not be normally distributed. Most of the results showed a significant improvement in the precision and accuracy on applying WR and NPR methods relative to LSPR.
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http://dx.doi.org/10.1007/s00216-013-6859-4DOI Listing
May 2013

Kinetic spectrophotometric methods for the determination of artificial sweetener (sucralose) in tablets.

Drug Test Anal 2011 Apr 29;3(4):214-20. Epub 2010 Dec 29.

Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria 21521, Egypt.

Two simple and sensitive kinetic spectrophotometric methods for the determination of sucralose are described. The first method is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time of 30 min. The absorbance of the green coloured manganate ions produced was measured at 610 nm. The second method is based on the reaction of sucralose with cerium (IV) ammonium sulfate in the presence of perchloric acid with the subsequent measurement of the excess unreacted cerium (IV) ammonium sulfate at 320 nm at a fixed time of 30 min in a thermostated water bath at 60 ± 1 °C. This principle is adopted to develop a kinetic method for sucralose determination. The absorbance concentration plots in both methods were rectilinear over the range 4-16 and 10-30 µg ml(-1) , for the first and second methods, respectively. The different experimental parameters affecting the development and stability of the colours were carefully studied and optimized. The determination of sucralose by rate constant method, fixed concentration method, and fixed-time method was also feasible with calibration equations obtained but the latter method was found to be more applicable. The two methods have been applied successfully to commercial tablets.
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http://dx.doi.org/10.1002/dta.208DOI Listing
April 2011

Non-parametric linear regression of discrete Fourier transform convoluted chromatographic peak responses under non-ideal conditions of internal standard method.

Talanta 2010 Nov 29;83(1):93-109. Epub 2010 Sep 29.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, El-Messalah, Alexandria 21521, Egypt.

This manuscript discusses the application of chemometrics to the handling of HPLC response data using the internal standard method (ISM). This was performed on a model mixture containing terbutaline sulphate, guaiphenesin, bromhexine HCl, sodium benzoate and propylparaben as an internal standard. Derivative treatment of chromatographic response data of analyte and internal standard was followed by convolution of the resulting derivative curves using 8-points sin x(i) polynomials (discrete Fourier functions). The response of each analyte signal, its corresponding derivative and convoluted derivative data were divided by that of the internal standard to obtain the corresponding ratio data. This was found beneficial in eliminating different types of interferences. It was successfully applied to handle some of the most common chromatographic problems and non-ideal conditions, namely: overlapping chromatographic peaks and very low analyte concentrations. For example, a significant change in the correlation coefficient of sodium benzoate, in case of overlapping peaks, went from 0.9975 to 0.9998 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. Also a significant improvement in the precision and accuracy for the determination of synthetic mixtures and dosage forms in non-ideal cases was achieved. For example, in the case of overlapping peaks guaiphenesin mean recovery% and RSD% went from 91.57, 9.83 to 100.04, 0.78 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. This work also compares the application of Theil's method, a non-parametric regression method, in handling the response ratio data, with the least squares parametric regression method, which is considered the de facto standard method used for regression. Theil's method was found to be superior to the method of least squares as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points. For the purpose of comparison, the results obtained using the above described internal standard method were compared with the external standard method for all types of linearity.
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http://dx.doi.org/10.1016/j.talanta.2010.08.046DOI Listing
November 2010

Determination of etofibrate, fenofibrate, and atorvastatin in pharmaceutical preparations and plasma using differential pulse polarographic and square wave voltammetric techniques.

J AOAC Int 2008 Sep-Oct;91(5):1051-8

University of Alexandria, Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, Alexandria, Egypt.

Etofibrate, fenofibrate, and atorvastatin were determined in their pharmaceutical preparations and human plasma using differential pulse polarographic and square wave voltammetric techniques by reduction at a dropping-mercury working electrode versus Ag/AgCl reference electrode. The reversibility of the electrode reactions was tested using cyclic voltammetry, and they were found to be irreversible reduction reactions. Optimum conditions such as pH, scan rate, and pulse amplitude were studied, and validation of the proposed methods was performed. The proposed methods proved to be accurate, precise, robust, and specific for determination of the 3 drugs. The relative standard deviation values were <2%, indicating that these methods are precise. Limits of detection and quantitation were in the ranges of 0.037-0.21 and 0.12-0.71 microg/mL, respectively, indicating high sensitivity.
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December 2008

Non-parametric linear regression of discrete Fourier transform convoluted chromatographic peak responses in non-ideal conditions.

Talanta 2005 May;66(4):1073-87

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, El-Mesala, Alexandria 21521, Egypt.

This manuscript discusses the application of chemometrics to the handling of HPLC response data using a model mixture containing ascorbic acid, paracetamol and guaiphenesin. Derivative treatment of chromatographic response data followed by convolution of the resulting derivative curves using 8-points sinx(i) polynomials (discrete Fourier functions) was found beneficial in eliminating different types of interferences. This was successfully applied to handle some of the most common chromatographic problems and non-ideal conditions, namely: very low analyte concentrations, overlapping chromatographic peaks and baseline drift. For example, a significant change in the correlation coefficient of guaiphenesin, in case of baseline drift, went from 0.9978 to 0.9998 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. It also compares the application of Theil's method, a non-parametric regression method, in handling the response data, with the least squares parametric regression method, which is considered the de facto standard method used for regression. Theil's method was found to be superior to the method of least squares as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points.
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http://dx.doi.org/10.1016/j.talanta.2005.01.008DOI Listing
May 2005

Non-parametric linear regression of discrete Fourier transform convoluted densitometric peak responses.

J Pharm Biomed Anal 2006 Mar 27;40(5):1048-56. Epub 2005 Oct 27.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt.

The manuscript discusses the application of chemometrics to the handling of TLC response time data. Derivative treatment of chromatographic response data followed by convolution of the resulting derivative curves using 8-points sinx(i) polynomials (discrete Fourier functions) was found to be beneficial in eliminating the interference due to background noise in TLC-densitometric measurements. It also compares the application of Theil's method, a non-parametric regression method, in handling the response data, with the least squares parametric regression method, which is considered the de facto standard method used for regression. Theil's method was found to be superior to the method of least squares as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points.
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http://dx.doi.org/10.1016/j.jpba.2005.08.037DOI Listing
March 2006

High performance liquid chromatographic determination of some co-administered anticancer drugs in pharmaceutical preparations and in spiked human plasma.

J Pharm Biomed Anal 2004 Mar;34(5):1099-107

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt.

Two HPLC methods are introduced in this paper for the simultaneous determination of doxorubicin hydrochloride (DOX) and 5-fluorouracil (5-FU), combination I, and of cytarabine (CYT) and etoposide (ETO), combination II, as co-administered drugs. In both combinations, a [250 mm x 4.6 mm C-18 column is used. The mobile phase for combination I consists of a mixture of acetonitrile and 0.05 M disodium hydrogenphosphate (50:50, v/v) containing 0.1% sodium laurylsulfate (SLS) adjusted to pH 3.7 at a flow rate 1 ml/min, with UV detection at 260 nm and ambient temperature. For combination II, the mobile phase consists of a mixture of 0.02 M sodium dihydrogenphosphate aqueous solution adjusted to pH 6.0 (with 0.2 M orthophosphoric acid or sodium hydroxide) and acetonitrile in a ratio of (7:3) at a flow rate 1 ml/min, with UV detection at 254 nm and ambient temperature. The methods also permitted the determination of methyl hydroxybenzoate (MHB) which is used as a preservative in DOX vials, combination I, and of benzyl alcohol (BZA) preservative in ETO vials, combination II. The proposed HPLC methods were successfully applied to the determination of the investigated drugs, of the two combinations, both in injection solutions and spiked human plasma samples with high precision and accuracy. Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are presented in the text.
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http://dx.doi.org/10.1016/S0731-7085(03)00655-1DOI Listing
March 2004
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