Simultaneous LC–MS Analysis of Paclitaxel and Retinoic Acid in Plasma and Tissues from Tumor-Bearing Mice

Abstract

A novel method has been developed for simultaneous analysis of paclitaxel (PTX) and retinoic acid (ATRA) in mice plasma and tissue homogenates. The analyte was isolated by liquid-liquid partitioning, to minimize analyte degradation, and fractions were analyzed by liquid chromatography-mass spectrometry (LC-MS). Liquid-liquid extraction with tert-butyl methyl ether was used for sample preparation and docetaxel was used as internal standard (IS). Separation of PTX, ATRA, and the IS was performed on a C 18 column with gradient elution and detection by use of a single-quadrupole mass spectrometer in selected-ion-monitoring mode. The method had high extraction recovery ([85%) and accuracy ([90%), with intra-day and inter-day precision \15%, and was rugged with good linearity. The limits of quantitation were determined to be 2 and 4 ng mL -1 for PTX and ATRA, respectively. Freeze-thaw stability, short-term stability, long-term stability, and sample stability in the autosampler tray were examined; this indicated freezing and thawing during bio-sample preparation should be avoided, but no other stability-related problems occurred during sample storage, extraction, and chromatography of PTX and ATRA in plasma and tissue samples. The assay was successfully used for simultaneous analysis of PTX and ATRA in mice plasma and different tissues to support pharmacokinetic and in-vivo distribution studies of the two drugs.

Pharmacokinetic and tissue distribution of paclitaxel in rabbits assayed by LC‐UV after intravenous administration of its novel liposomal formulation

“…In the development of LC‐UV analysis method for determination of PTX in patient's plasma, animal plasma and tissues, pre‐treatment of PTX in these bio‐samples was carried out by utilizing either PPT (Zhang et al ., , ; Beijnen et al ., ; Hou et al ., ) or solid‐phase extraction methods (Wang et al ., ; Green et al ., ). To our knowledge, rabbit tissue samples pre‐treated using the PPT method have not been reported.…”

“…Thus, it is necessary to develop and validate an analysis method to investigate the pharmacokinetics and tissue distribution of the novel liposomal formulation of PTX. A number of analytical methods of determining PTX in biological fluids and tissues have been reported, including liquid chromatography-mass spectrometry (LC-MS), in human, dog, rat, mouse plasma or tissues (Tan et al, 2006;Gardner et al, 2008;Bulitta et al, 2009;Jiang et al, 2009;Hou et al, 2011;Grobosch et al, 2012;NageswaraRao et al, 2012;Zhang et al, 2011), and high-performance liquid chromatography (HPLC) in plasma (Suno et al, 2007;Mowafy et al, 2012). Among these analytical methods, HPLC has been most frequently employed in the pharmacokinetic studies of PTX owing to its simplicity, sensitivity and selectivity.…”

Linear–Dendritic Copolymer Composed of Polyethylene Glycol and All-trans-Retinoic Acid as Drug Delivery Platform for Paclitaxel against Breast Cancer

“…Tumors were collected, washed with cold saline, dried over filter paper, weighed, and frozen at −20 °C until analysis. The PTX concentration in 10% (w/v) tumor homogenate was measured by LC/MS as described elsewhere …”

Design of a Paclitaxel Prodrug Conjugate for Active Targeting of an Enzyme Upregulated in Breast Cancer Cells

“…This confirms the formation of VIII in papain degradation of PGD in a buffer solution that contains sodium ion. Molecules with multiple oxygens, including PTX, are known to form sodium adducts. , Therefore, the molecular ion peak for VIII shows the replacement of a proton in VIII with a sodium ion, i.e., [M + Na] + at m / e 1350. Thus, PGD was shown to release paclitaxel–GFLG (VIII) in the presence of cathepsin B-like enzyme.…”