Determination of paclitaxel and related taxanes in bulk drug and injectable dosage forms by reversed phase liquid chromatography and micellar electrokinetic capillary chromatography.
Item
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Title
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Determination of paclitaxel and related taxanes in bulk drug and injectable dosage forms by reversed phase liquid chromatography and micellar electrokinetic capillary chromatography.
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Identifier
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AAI9820579
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identifier
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9820579
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Creator
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Shao, Lillian Kuangjing.
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Contributor
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Adviser: David C. Locke
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Date
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1998
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Analytical | Chemistry, Pharmaceutical
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Abstract
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Baseline resolution of 15 taxanes including paclitaxel is achieved on pentafluorophenyl HPLC columns. The methods developed are suitable for the determination of potency, content uniformity, and degradation profile of the paclitaxel bulk drug and injectable dosage form. Good resolution of taxanes from the excipient Cremophor EL (polyethoxylated castor oil) is achieved. The methods for the bulk drug and injectable form, were fully and partially validated respectively, according to USP guideline. The elution order of taxanes is related to molecular size, the number of acetylated hydroxyl groups, and the substitution of a xylosyl group at the 7-position. Thermodynamics of the separation were studied, and enthalpies of transfer, {dollar}\rm\Delta H\sp\circ,{dollar} determined. Conversion of a hydroxyl group to an acetyl group has a large effect on the {dollar}\rm\Delta H\sp\circ,{dollar} as does the addition of a xylosyl derivative to the 7-hydroxy.;Micellar electrokinetic capillary chromatographic technique is applied to the separation of 15 taxanes in 11.5 minutes. An aqueous acetonitrile buffer with SDS surfactant allows resolution of the 15 taxanes from each other and from the principal matrix ingredient, Cremophor EL, in the injectable dosage form. The migration order is apparently that of decreasing aqueous phase solubility, which is related to the presence of a side chain at the carbon-13 position; to the addition of a xylosyl group at the 7-position; to the number of acetylated hydroxyl groups; and to the increasing affinity of the taxane side chain for the micellar phase. The retention factor, k{dollar}\sp\prime,{dollar} increases linearly with SDS concentration above the CMC. With increasing concentration of ACN, k{dollar}\sp\prime{dollar} values for taxanes without a side chain decrease; for the most hydrophobic taxanes, k{dollar}\sp\prime{dollar} increases up to 20% (v/v) ACN and then decreases rapidly at higher concentrations. Similar behavior was observed with methanol but the break in k{dollar}\sp\prime{dollar} occurred between 30% and 40% (v/v). Resolution was unacceptably poor if samples dissolved in methanol were injected; samples dissolved in buffer containing SDS were well-behaved, probably because of stacking of the micelles during injection. The {dollar}\rm\Delta H\sp\circ{dollar} of transfer of taxanes from aqueous phase to micelle phase were determined.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
