High-performance liquid chromatography tandem mass spectrometry procedure with automated solid phase extraction sample preparation for the quantitative determination of paclitaxel (Taxol) in human plasma.
A sensitive, specific, accurate and reproducible analytical method was developed and validated for the quantitation of the anticancer agent paclitaxel in human plasma. This procedure is based on high performance liquid chromatography/ion spray-tandem mass spectrometry. This methodology is highly specific because a MS/MS technique (multiple reactant-ion monitoring, MRM) was used for both paclitaxel and its internal standard. The use of a fully automated solid phase extraction procedure, using a CN Sep-pak cartridge, to improve the detection limit and quantification limit of paclitaxel in human plasma samples, was evaluated. The method involves the addition of methyl-paclitaxel as internal standard (i.s.). The retention times of paclitaxel and the I.S. were 2.8 and 4.0 min., respectively. The assay was linear over the range 5 to 500 ng/mL, with a quantification limit of 5 ng/mL having a coefficient of variation (c.v.) < 10%. Standard calibration curves, performed on three different days, had correlation coefficients always greater than 0.998. The intra and inter-day precision were within 12%, and accuracy was included in the range 102-110%. Paclitaxel recovery assessed at 15,250 and 500 ng/mL, was determined to be greater than 85%. The assay is applicable to clinical pharmacokinetic studies.
Sottani
C
C
Laboratory of Environmental Hygiene and Industrial Toxicology, S. Maugeri Foundation, Pavia, Italy.
Minoia
C
C
D'Incalci
M
M
Paganini
M
M
Zucchetti
M
M
D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D017239:Paclitaxel / Q000097:blood* / Q000493:pharmacokinetics; D011786:Quality Control
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D017239:Paclitaxel