Quantitative analysis of Variolin analog (PM01218) in mouse and rat plasma by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
PM01218 is a novel marine-derived alkaloid and has shown potent growth inhibitory activity against several human cancer cell lines. A rapid and sensitive high performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to quantify PM01218 in mouse and rat plasma. The lower limit of quantitation (LLOQ) was 0.05 ng/mL. The calibration curve was linear from 0.05 to 100 ng/mL (R(2)>0.999). The assay was specifically based on the multiple reaction monitoring (MRM) transitions at m/z 278.4-->184.2, no endogenous material interfaced with the analysis of PM01218 and its internal standard from blank mouse and rat plasma. The mean intra- and inter-day assay accuracy remained below 15 and 8%, respectively, for all calibration standards and QC samples. The intra- and inter-day assay precision was less than 12.8 and 8.5% for all QC levels, respectively. The utility of the assay was demonstrated by pharmacokinetics studies of i.v. (bolus) PM01218 on SD rats.
Yin
Jianming
J
PharmaMar USA Inc., 320 Putnam Avenue, Cambridge, MA 02139-4616, USA. jyin@pharmamarusa.com
Aviles
Pablo
P
Ly
Carl
C
Lee
William
W
Guillen
Maria Jose
MJ
Munt
Simon
S
Cuevas
Carmen
C
Faircloth
Glynn
G
D000818:Animals; D001372:Aza Compounds / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D008297:Male; D051379:Mice; D011743:Pyrimidines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D001372:Aza Compounds; D011743:Pyrimidines; C474921:variolin B