Liquid chromatography/tandem triple‐quadrupole mass spectrometry for determination of paclitaxel in rat tissues

Abstract

A liquid chromatography/tandem triple-quadrupole mass spectrometry assay to quantify paclitaxel in rat tissue homogenates containing taxol or paclitaxel nanoliposome (PTX-NLP) was developed and validated. Liquid-liquid extraction with tert-butyl methyl ether was used for tissue sample preparation and docetaxel was used as the internal standard. Paclitaxel and docetaxel were separated on a 200 mm x 4.6 mm x 5 microm C(18) column and quantified using a triple-quadrupole mass spectrometer operating in positive ion electrospray selective reaction monitoring mode (ESI(+)-SRM) with a total run time of 6.0 min. The peak area of the m/z 876.3 --> 307.9 transition of paclitaxel is measured versus that of the m/z 830.3 --> 549.1 transition of docetaxel to generate the standard curves. The standard curves were linear over the concentration range of 0.2008-2008 ng/mL for different tissues. The method had high extraction recovery (>90%) and accuracy (>90%) with the intra-day and inter-day precision <15%. Frozen stability, freeze/thaw stability, extraction stability and solution stability at ambient temperature were examined, which indicated the tissue samples should be extracted within 5 days and avoid being frozen and thawed repeatedly over 5 times. Extracted samples after evaporation could be stored at -20 degrees C for 20 days without drug degradation and no degradation was also observed after solution samples were left to stand at ambient temperature for 24 h. This assay was used to support an in vivo biodistribution study of PTX-NLP in rats.

Determination of main taxoids in Taxus species by microwave‐assisted extraction combined with LC‐MS/MS analysis

“…The collision energy were optimized for the six taxoids. It is 40 286.1 for 7-epi-10-DAT. Quantitative analysis was carried out using peak areas obtained from the MRM.…”

Quantification of Taxanes in Biological Matrices: A Review of Bioanalytical Assays and Recommendations for Development of New Assays

“…Bioanalytical assays for quantification of paclitaxel [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] (SupplemenTary Table 2), paclitaxel and its metabolites [71][72][73][74][75] (SupplemenTary Table 3), or paclitaxel and other drugs (including docetaxel) [76][77][78][79][80][81][82] (S upplemenTary Table 5) by LC-MS/MS are widely described. For quantification of docetaxel [83][84][85][86][87][88][89][90], docetaxel and its metabolites [91,92] (SupplemenTary Table 4), or docetaxel and other drugs [93][94][95] (Supplemen- Tary Table 5), fewer assays are published.…”

Lack of stability of topotecan in heart tissue homogenates: is it an analytical dilemma or a real phenomenon?

“…Also, it helps the analyst to work within a pre-specified boundary to ensure data integrity. For example, in another published work related to tissue distribution of paclitaxel, Tong et al (2006) have proposed that rat tissue homogenate samples should not be subjected to more than five freeze-thaw cycles as part of the validation protocol, whereas Baranda et al (2006) have proposed stringent conditions for sample handling and processing to prevent the extraordinary photodegradation of calcium channel antagonists belonging to the class 1,4-dihydropyridines, namely nifedipine, nisoldipine, etc., through validation protocols.…”