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Tawakol A. El-Shourbagy

Bio: Tawakol A. El-Shourbagy is an academic researcher from Abbott Laboratories. The author has contributed to research in topics: Sample preparation & Liquid chromatography–mass spectrometry. The author has an hindex of 18, co-authored 37 publications receiving 1377 citations.

Papers
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Journal ArticleDOI
TL;DR: The most recent advances in sample preparation, separation, and the mass spectrometric aspects of high-throughput quantitative bioanalysis of drug and metabolites in biological matrices are reviewed.

475 citations

Journal ArticleDOI
TL;DR: A new sample preparation technique, salting-out assisted liquid-liquid extraction with acetonitrile, for high-throughput good laboratory practice sample analysis using LCMS, which indicates that the method is rapid, reliable and suitable for regulated bioanalysis.
Abstract: Acetonitrile, an organic solvent miscible with aqueous phase, has seen thousands of publications in the literature as an efficient deproteinization reagent. The use of acetonitrile for liquid-liquid extraction (LLE), however, has seen very limited application due to its miscibility with aqueous phase. The interest in LLE with acetonitrile has been pursued and reported in the literature by significantly lowering the temperature of the mixture or increasing the salt concentration in the mixture of acetonitrile and aqueous phase, resulting in the separation of the acetonitrile phase from aqueous phase, as observed in conventional LLE. However, very limited application of these methods has been reported. The throughput was limited. In this report, we report a new sample preparation technique, salting-out assisted liquid-liquid extraction with acetonitrile, for high-throughput good laboratory practice sample analysis using LCMS, Two compounds from an approved drug, Kaletra, were used to demonstrate the extractability of drugs from human plasma matrix. Magnesium sulfate was used as the salting-out reagent. Extracts were diluted and then injected into a reversed phase LC-MS/MS system directly. One 96-well plate was extracted with this new approach to evaluate multiple parameters of a good laboratory practice analytical method. Results indicate that the method is rapid, reliable and suitable for regulated bioanalysis. With minimal modification, this approach has been used for high-throughput good laboratory practice analysis of a number of compounds under development at Abbott.

124 citations

Journal ArticleDOI
TL;DR: The assay has proven rugged and specific and has been employed to generate data in support of preclinical studies and could be used for the development of bioanalytical assays to provide preclinical and clinical support for other protein drug candidates and, furthermore, for the validation of biomarkers discovered from proteomic research.
Abstract: Immunoassays are used extensively in the quantitative analysis of proteins in plasma, urine, and other biological matrixes to support preclinical and clinical studies. Although immunoassays are both sensitive and rapid, difficulties during development of these assays are compounded by the need to have a specific antibody or antigen to the protein of interest. Furthermore, calibration curves of immunoassays are inherently nonlinear, and the technique often detects many structurally related components in addition to the analyte of interest. We have developed a novel strategy of analyzing protein concentrations in plasma by utilizing 96-well solid-phase extraction and LC-MS/MS detection of the intact protein. This strategy has been successfully applied in method development and assay validation of quantitatively analyzing protein rK5 concentrations in monkey plasma samples. Additional techniques such as precolumn regeneration and column heating were also incorporated into the assay. Total run time for each sample was approximately 15 min. An LLOQ of 99.2 ng/mL from a sample volume of 50 microL, corresponding to only 380 fmol (3.97 ng) of the rK5 analyte being injected onto the analytical column (assuming 100% extraction recovery), was obtained. The validated linear dynamic range was between 99.2 and 52 920.0 ng/mL, with a correlation coefficient (r(2)) ranging from 0.9972 and 0.9994. The intraassay CV for this assay was between 0.6 and 3.8%, and the interassay CV was between 1.7 and 3.2%. Interassay mean accuracies were between 101.5 and 104.7%. The assay has proven rugged and specific and has been employed to generate data in support of preclinical studies. This strategy for rK5 assay could be used for the development of bioanalytical assays to provide preclinical and clinical support for other protein drug candidates and, furthermore, for the validation of biomarkers discovered from proteomic research.

81 citations

Journal ArticleDOI
TL;DR: The use of a mass spectrometry friendly organic salt, ammonium acetate, is reported for the first time, as a salting-out reagent in SALLE with acetonitrile for the simultaneous quantitation of an Abbott investigational new drug ABT-869 and its hydrophilic metabolite in human plasma.

80 citations

Journal ArticleDOI
TL;DR: A high-throughput salting-out assisted liquid/liquid extraction (SALLE) method with acetonitrile and mass spectrometry compatible salts for simultaneous LC-MS/MS analysis of SS and SSA was used for a bioequivalence study.

71 citations


Cited by
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Journal ArticleDOI
TL;DR: In this paper, the origins and the fundamentals of green analytical chemistry (GAC) are discussed, and the strategies and the tools available to make sample-pretreatment and analytical methods greener.
Abstract: We discuss the origins and the fundamentals of Green Analytical Chemistry (GAC), based on the literature published about clean, environmentally-friendly or GAC methods. We pay special attention to the strategies and the tools available to make sample-pretreatment and analytical methods greener. We consider that the main principles are to replace toxic reagents, to miniaturize and to automate methods, making it possible to reduce dramatically the amounts of reagents consumed and wastes generated, so reducing or avoiding side effects of analytical methods. We also consider on-line decontamination or passivation of wastes to be of special interest in making analytical chemistry sustainable.

806 citations

Journal ArticleDOI
TL;DR: In this review, the influence of matrix effects on bioanalytical LC-MS/MS methods is discussed and illustrated with some examples, and possible solutions to reduce or eliminate matrix effects are highlighted.

692 citations

Journal Article
TL;DR: Rapamycin is a new antifungal antibiotic produced by Streptomyces hygroscopicus and can be classified as a triene, highly active against various Candida species, especially Candida albicans.
Abstract: : Rapamycin is a new antifungal antibiotic produced by Streptomyces hygroscopicus NRRL 5491. It was isolated from the mycelium by solvent extraction, purified by silica gel column chromatography and crystallized as a colorless solid which melts at 183 approximately to 185 degrees C and has the empirical formula C56H89NO14. From its characteristic ultraviolet absorption spectrum rapamycin can be classified as a triene. It is highly active against various Candida species, especially Candida albicans. Its activity is compared with that of amphotericin B, candicidin and nystatin.

639 citations

Journal ArticleDOI
TL;DR: This review gives a detailed description on when matrix effects (ME) might be expected, and how they can be evaluated, and the main strategies to overcome these phenomena are described in detail.
Abstract: Matrix-dependent signal suppression or enhancement represents a major drawback in quantitative analysis with liquid chromatography coupled to atmospheric pressure ionization mass spectrometry (LC-API-MS). Because matrix effects (ME) might exert a detrimental impact on important method parameters (limit of detection, limit of quantification, linearity, accuracy, and precision), they have to be tested and evaluated during validation procedure. This review gives a detailed description on when these phenomena might be expected, and how they can be evaluated. The major sources of ME are discussed and illustrated with examples from bioanalytical, pharmaceutical, environmental, and food analysis. Because there is no universal solution for ME, the main strategies to overcome these phenomena are described in detail. Special emphasis is devoted to the sample-preparation procedures as well as to the recent improvements on chromatographic and mass spectrometric conditions. An overview of the main calibration techniques to compensate for ME is also presented. All these solutions can be used alone or in combination to retrieve the performance of the LC-MS for a particular matrix-analyte combination.

631 citations

Journal ArticleDOI
TL;DR: UHPLC has recently become a wide-spread analytical technique in many laboratories which focus on fast and sensitive bio-analytical assays and the key advantages are the increased speed of analysis, higher separation efficiency and resolution, higher sensitivity and much lower solvent consumption as compared to other analytical approaches.

519 citations