2. 4,4'-Butane-1,4-diylbis[3-ethyl-1H-1,2,4-triazol-5(4H)-one] and 4-hydroxy-3-n-propyl-1H-1,2,4-triazol-5(4H)-one
Nazan Ocak Iskeleli, Samil Işik, Kemal Sancak, Selami Saşmaz, Yasemin Unver, Mustafa Er Acta Crystallogr C. 2005 Jun;61(Pt 6):o363-5. doi: 10.1107/S0108270105008449. Epub 2005 May 13.
The title compounds, C12H20N6O2, (I), and C5H9N3O2, (II), display the characteristic features of 1,2,4-triazole derivatives. Compound (I) lies about an inversion centre which is at the mid-point of the central C-C bond. Compound (II) also contains a planar 1,2,4-triazole ring but differs from (I) in that it has a hydroxy group attached to the ring. Molecules of (I) are held together in the crystal structure by intermolecular N-H...O contacts and by weak pi-pi stacking interactions between the 1,2,4-triazole moieties. Compound (II) contains intermolecular O-H...O and N-H...O hydrogen bonds.
3. Quantitative determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'-biphenyl]-4-yl)ethyl)propane-1,3-diol and its active phosphorylated metabolite in rat blood by LC-MS/MS and application to PK/PD analysis
Manman Zhao, Jiaqi Mi, Dan Li, Xin Liu, Shuang Yang, Baolian Wang, Li Sheng, Xiaojian Wang, Jing Jin, Jinping Hu, Yan Li Anal Bioanal Chem. 2015 Sep;407(24):7511-6. doi: 10.1007/s00216-015-8924-7. Epub 2015 Aug 22.
A sensitive and specific LC-MS/MS method was developed and validated for simultaneous determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'-biphenyl]-4-yl)ethyl)propane-1,3-diol (SYL930) and its active phosphate metabolite (SYL930-P) in rat blood using SYL927, an analogue of SYL930 as the internal standard. Blood samples were prepared by a simple protein precipitation with acetonitrile. The chromatographic separation was performed on a ZorbaxSB-C18 column (3.5 μm, 2.1 × 100 mm) with a gradient mobile phase of methanol/water containing 0.1 % formic acid (v/v) at a flow rate of 0.2 mL/min. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) in multiple reactions monitoring mode (MRM). The monitored transitions were 381.2 → 364.2 for SYL930, 461.2 → 334.2 for SYL930-P, and 367.1 → 350.4 for the internal standard, respectively. Good linearity was obtained for the analytes over the range of 0.2-100 ng/mL for SYL930 and 0.5-100 ng/mL for SYL930-P. The lower limits of quantitation (LLOQs) for SYL930 and SYL930-P were 0.2 and 0.5 ng/mL, respectively. The intra-day and inter-day precisions (RSD, %) of analytes were within 9.87 %, and the accuracy (RE, %) ranged from -7.04 to 13.15 %. The mean recoveries for two compounds in rat blood were 87.9-109 %. The analytes were proved to be stable during all sample storage, preparation, and analytic procedures. The validated method was successfully applied to pharmacokinetic and PK/PD studies of SYL930 and SYL930-P in rats after oral administration of SYL930. Graphical Abstract Quantitative determination of SYL930 and its active phosphorylated metabolite in rat blood by LCMS/MS and application to PK/PD analysis.
