ABSTRACT
BACKGROUND: A novel, sensitive and specific LC-MS/MS technique was developed and validated for the quantification of fostemsavir in human plasma and its pharmacokinetic application in rabbits. METHODS: Chromatographic separation of the fostemsavir and fosamprenavir (internal standard) were achieved on Zorbax C18 (50 mm × 2 mm × 5 µm) column with 0.80 mL/min flow rate and coupled with API6000 triple quadrupole MS in multi reaction monitoring mode by applying mass transitions m/z 584.16/105.03 for fostemsavir and m/z 586.19/57.07 for the internal standard. RESULTS: The calibration curve exhibited linearity in concentration range of 58.5-2340.0 ng/mL for fostemsavir. The LLOQ was 58.5 ng/mL. The validated LC-MS/MS process was effectively applied for the analysis of plasma in healthy rabbits for determinations of Fostemsavir. From the pharmacokinetic data, the mean of Cmax and Tmax were 198.19 ± 5.85 ng/mL and 2.42 ± 0.13, respectively. Plasma concentration reduced with t1/2 of 7.02 ± 0.14. AUC0âLast value obtained was 2374.87 ± 29.75 ng. h/ml, respectively. CONCLUSION: In summary, the developed method has been successfully validated and pharmacokinetic parameters were demonstrated after oral administration of Fostemsavir to healthy rabbits.
Subject(s)
Piperazines , Tandem Mass Spectrometry , Animals , Humans , Rabbits , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Plasma , Reproducibility of ResultsABSTRACT
A series of new N-pyrazolylbenzamides (5a-x) were synthesized by aroylation of 5-amino-1-phenyl-3-tbutylpyrazole. The structures of synthesized compounds were established based on spectral (FTIR, (1)H NMR, ESI Mass) analysis and purity was ascertained by HPLC. The antibacterial screening revealed that seven molecules exhibited an excellent antibacterial activity and eight compounds demonstrated considerable antifungal activity. Three molecules of the series 5e, 5s and 5w were found to be highly effective against Klebsilla pneumoneia with MIC of 3.12 µg/ml. Compounds 5b, 5f, 5g and 5o exhibited significant antitubercular activity with MIC of 12.5 µg/ml.
