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      Determination of a new polymer-bound paclitaxel derivative (PNU 166945), free paclitaxel and 7-epipaclitaxel in dog plasma and urine by reversed-phase high-performance liquid chromatography with UV detection.

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      Journal of chromatography. A

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          Abstract

          A sensitive and selective high-performance liquid chromatographic method for the determination of PNU 166945, a new polymer-bound paclitaxel derivative, free paclitaxel and 7-epipaclitaxel in dog plasma and urine has been developed. The method involves a solid-phase extraction of free paclitaxel and its possible degradation product 7-epipaclitaxel from plasma and urine, previously buffered with an equal volume of 0.05 M or 1 M KH2PO4 respectively, on 1-ml cyanopropyl columns. Cartridges elution was performed with the mobile phase, 0.05 M (pH 4.6) monobasic potassium phosphate-acetonitrile mixture (45:55, v/v). The samples were chromatographed on a reversed-phase octyl 4-microns column with UV detection at 229 nm. The retention times of paclitaxel and 7-epipaclitaxel were about 14 and 22 min, respectively. Determination of total paclitaxel (free + polymer-bound) was performed after release of paclitaxel from the polymeric carrier by chemical hydrolysis at room temperature (22 degrees C) for 20 h. After addition of 0.5 ml of methanol-0.1 M KH2PO4 mixture (50:50, v/v, pH = 7.5) to 0.5 ml of plasma or urine, paclitaxel was analysed as described above. PNU 166945 concentration was then determined by subtraction of free from total paclitaxel. The linearity, precision, accuracy and recovery of the method were evaluated. The limit of quantitation of the method was 5 ng/ml for biological fluid for paclitaxel and 7-epipaclitaxel and 20 ng/ml for PNU 166945 (as paclitaxel equivalent).

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          Author and article information

          Journal
          J Chromatogr A
          Journal of chromatography. A
          0021-9673
          0021-9673
          Feb 27 1998
          : 797
          : 1-2
          Affiliations
          [1 ] Pharmacia & Upjohn, Pharmacokinetics & Metabolism Department, Milan, Italy.
          Article
          S0021-9673(97)01204-1
          9542121
          41c3be27-a6c5-46bd-8844-226c00038e73
          History

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