Paclitaxel quantification in mouse plasma and tissues containing liposome-entrapped paclitaxel by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetics study.
A liquid chromatography-tandem mass spectrometry assay to quantify total paclitaxel in mouse plasma and tissue homogenates containing paclitaxel, Taxol, or liposome-entrapped paclitaxel-easy to use (LEP-ETU) was developed and validated. Docetaxel was used as the internal standard (IS). Liquid-liquid extraction with tert-butyl methyl ether was used for plasma sample preparation, and a one-step protein precipitation with acetonitrile containing 0.1% acetic acid was developed for tissue homogenates. Paclitaxel and IS are separated on a 50 x 2.1-mm C18 column and quantified using a triple-quadrupole mass spectrometer operating in positive ion electrospray multiple reaction monitoring mode, with a total run time of 3.5 min. The peak area of the m/z 854.4--> 286.2 transition of paclitaxel is measured versus that of the m/z 808.5--> 527.5 transition of IS to generate the standard curve. In plasma, the linear range is 0.2-500 ng/mL and could be extended by dilution to 100,000 ng/mL with acceptable precision and accuracy (< or = 15%). The lower limit of quantification is 0.5 ng/mL in tissue homogenates (10 ng/g tissue), and the standard curve is linear up to 1000 ng/mL, with precision and accuracy < or = 15%. This assay was used to support a pharmacokinetics and tissue distribution study of LEP-ETU in mice.
Guo
Wei
W
Pharmacokinetics, Safety, and Efficacy Department, Research & Development, NeoPharm, Inc., 1850 Lakeside Drive Waukegan, IL 60085, USA.
Johnson
Jenifer L
JL
Khan
Sumsullah
S
Ahmad
Ateeq
A
Ahmad
Imran
I
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D005615:Freezing; D007201:Indicator Dilution Techniques; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D015394:Molecular Structure; D017239:Paclitaxel / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013696:Temperature
D008081:Liposomes; D017239:Paclitaxel