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.
PharmaMar USA Inc., 320 Putnam Avenue, Cambridge, MA 02139-4616, USA. jyin@pharmamarusa.com
Jianming
J
Yin
Pablo
P
Aviles
Carl
C
Ly
William
W
Lee
Maria Jose
MJ
Guillen
Simon
S
Munt
Carmen
C
Cuevas
Glynn
G
Faircloth
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