Quantitative determination of total and unbound paclitaxel in human plasma following Abraxane treatment.
A simple, rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay was developed and validated for the quantification of both unbound and total paclitaxel in plasma following treatment with Abraxane (ABI-007) or Taxol. Accurate and reproducible analysis of ABI-007, an albumin nanoparticle formulation of paclitaxel could not be achieved using previously published methodology designed for Taxol. The final validated method involved protein precipitation followed by vacuum filtration, in a 96-well format for rapid processing. The 4min run employed gradient elution on a Waters SymmetryShield C8 (2.1mmx50mm, 3.5microm) column, followed by tandem mass spectrometric detection, in electrospray positive mode. Calibrator samples were prepared daily with paclitaxel and analyzed with both ABI-007 and paclitaxel quality control samples. To measure unbound drug, sample preparation was preceded by ultrafiltration. The assay was linear over the range of 10-2500ng/mL, with dilution providing measurement up to 50,000ng/mL. Within-run and between-run precision for all QC samples was less than 5.0% and 10.4%, respectively. Accuracy was high, with deviation of less than 6.1% for all QCs. Measurement of unbound paclitaxel was precise (BRP and WRP <10%).
Gardner
Erin R
ER
Clinical Pharmacology Program, SAIC-Frederick Inc., NCI-Frederick, MD 21702, USA.
Dahut
William
W
Figg
William D
WD
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000097:blood / Q000627:therapeutic use*; D002138:Calibration; D006801:Humans; D017239:Paclitaxel / Q000097:blood* / Q000627:therapeutic use; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D017239:Paclitaxel