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. (C) 1998 John Wiley & Sons, Ltd.

High-performance liquid chromatography tandem mass spectrometry procedure with automated solid phase extraction sample preparation for the quantitative determination of paclitaxel (Taxol (R)) in human plasma

D'Incalci M;
1998-01-01

Abstract

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. (C) 1998 John Wiley & Sons, Ltd.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/67432
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 61
  • ???jsp.display-item.citation.isi??? 58
social impact