Expedient liquid chromatographic assay for paclitaxel in plasma after its administration to cancer patients.
A rapid and expedient liquid chromatographic method for the analysis of paclitaxel in plasma is described. Paclitaxel and the internal standard (IS, N-nitrosodiphenylamine) were separated on a 10-microns particle, 8 mm x 10 cm C18 cartridge in conjunction with a radial compression system preceded by Guard Pak with a C18 insert. The mobile phase was a mixture of 1 mM sodium phosphate buffer (pH 5) and acetonitrile (55.5:45.5 per volume), and the flow rate was 4.5 ml/min. The compounds were extracted from plasma with ethyl acetate and were detected in the effluent spectrophotometrically at 227 nm. The recovery of paclitaxel from plasma at concentrations equivalent to 50, 400, and 800 micrograms/L paclitaxel in plasma was 79.1, 75.2, and 74.3%, respectively, and the retention times of the drug and IS under these conditions were 5.26 and 6.45 min, respectively. The relationship between the concentration and peak height ratio (drug/IS) was linear (r = 0.9938-0.9998) in the range of 10-1,600 micrograms/L, and no interference in the assay was observed. The intrarun coefficient of variations (CV) at 50, 250, and 800 micrograms/L were 4.9, 5.4, and 4.1%, respectively, and the deviations from theoretical accuracy at these concentrations were 1.2, 0.5, and 5.4%, respectively. We are currently using this assay to investigate the pharmacokinetics of paclitaxel in cancer patients treated with this agent in a combined chemotherapy.
el-Yazigi
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Pharmacokinetics Laboratory, Biological and Medical Research Department, Riyadh, Saudi Arabia.
Yusuf
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D000097:Acetonitriles / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D009602:Nitrosamines / Q000097:blood; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D013056:Spectrophotometry, Ultraviolet
D000097:Acetonitriles; D000972:Antineoplastic Agents, Phytogenic; D009602:Nitrosamines; C023649:N-nitrosodiphenylamine; D017239:Paclitaxel; C032159:acetonitrile