Use of liquid chromatography-tandem mass spectrometry for the analysis of pentoxifylline and lisofylline in plasma.
A method was developed for the quantitation of pentoxifylline [1-(5-oxohexyl)-3,7-dimethylxanthine] and a primary active metabolite, lisofylline [1-(5-hydroxyhexyl)-3,7-dimethylxanthine], using high-performance liquid chromatography (HPLC)-tandem mass spectrometry. This method was developed in order to overcome problems encountered with HPLC-ultraviolet detection. The operating parameters of the electrospray interface (PE SCIEX, TurboIon Spray) and lens voltages of the triple-quadrupole detector (PE SCIEX 365) were optimized in positive ion mode to obtain the best sensitivity of the analytes. Collision-induced dissociation was used to produce fragment ions, and multiple reaction monitoring was used to quantitate pentoxifylline (m/z 279/181) and lisofylline (m/z 263/181). Dichloromethane was used to extract the drug, metabolite, and the internal standard (3-isobutyl-1-methylxanthine) from plasma. A reverse-phase C8(2) 150 x 1.0 mm HPLC column was used to resolve all three compounds in less than 6 min. Calibration curves were generated using peak area and were linear from 1 to 1000 ng/mL (R(2) > 0.99). The small sample volume, ease of extraction, and sensitivity provide advantages over more conventional methods of quantitation.
Kyle
Patrick B
PB
Department of Pharmacology and Toxicology University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. pkyle@pharmacology.umsmed.edu
Adcock
Kim G
KG
Kramer
Robert E
RE
Baker
Rodney C
RC
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000097:blood*; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
C025189:lisofylline; D010431:Pentoxifylline