RESUMO
BACKGROUND: Accurate and selective LC/ESI-MSMS method development and validation for the quantitation of pacritinib is the primary goal of this study to perform kinetic studies in the healthy rabbit. METHODS: Chromatographic resolution was accomplished with a hypersil/ODS (50â¯mmâ¯×â¯4.6â¯mm, 3⯵) analytical C18 column and a mobile phase composition of 0.1% formic acid and ACN in the proportion of 25:75 with a 0.6â¯ml/min flow of the mobile phasic system from the analytical column. The method was employed by monitoring the established ionic transitions of m/z-473.25/98.09 for Pacritinib and 506.18/57.12 for the internal standard (Amprenavir) in multiple reaction monitoring. RESULTS: The calibration plot regression line was yâ¯=â¯0.0002×â¯+â¯0.007, with a correction coefficient (r2) of 0.9989. The CV outcomes for the matrix effect at low-QC and high-QC levels were 4.79% and 4.91%, respectively. The percentage average recoveries for Pacritinib in High-QC (12.70⯵g/ml), MQC (8.50⯵g/ml), and Low-QC (1.19⯵g/ml) were 95.87%, 103.64%, and 94.32%, respectively. The obtained values were found between 2.98 and 5.07% for the QC (1.19, 8.50, and 12.70⯵g/ml) samples. The established procedure was subjected to kinetics study of Pacritinib after oral administration in rabbits. Cmax, Tmax, and T1/2, of the Pacritinib tablets were 247.25⯱â¯3.32â¯ng/ml, 6.0⯱â¯0.03â¯h, and 12.24⯱â¯0.53â¯h, respectively. AUC0-∞ infinity for Pacritinib tablets was 1691.74⯱â¯3.67â¯ngâ¯h/ml. CONCLUSION: After oral administration of Pacritinib to healthy rabbits, pharmacokinetic characteristics were presented, and the established technique was effectively verified.
RESUMO
Cryptophycin-38 (2), -326 (3), and -327 (4) are three new trace constituents of the terrestrial cyanobacterium Nostoc sp. GSV 224. Cryptophycin-38 is a stereoisomer of cryptophycin-1 (1) and to date is the only naturally occurring analogue that possesses a S,S epoxide group in unit A. Cryptophycin-327 is a geometric isomer that differs from 1 in having a cis Delta(2)-double bond in unit A. Cryptophycin-326 is related to cryptophycin-21, but has two chlorines ortho to the methoxy group in unit B. The relative and absolute stereochemistries of 2 have been related to known cryptophycins by semisynthesis and/or spectral analysis.