Simultaneous determination of six bioactive components of total flavonoids of Scorzonera austriaca in rat tissues by LC-MS/MS: application to a tissue distribution study

ABSTRACT A liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of six bioactive constituents including vitexin, orientin, isoorientin, 2"-O-β-D-xylopyranosyl isoorientin, 2"-O-β-D-xylopyranosyl isovitexin, and 6-C-L-α-arabipyranosyl vitexin in rats' various tissues using isoquercitrin as the internal standard. Biological samples were pretreated by protein precipitation with acetonitrile. Chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. All analytes and internal standard were quantitated through electrospray ionization in negative ion selected reaction monitoring mode. The mass transitions were as follows: m/z 431 → 311 for vitexin, m/z 447 → 327 for orientin or isoorientin, m/z 579 → 459 for 2"-O-β-D-xylopyranosyl isoorientin, m/z 563 → 293 for 2"-O-β-D-xylopyranosyl isovitexin, m/z 563 → 353 for 6-C-L-α-arabipyranosyl vitexin, and m/z 463 → 300 for the internal standard, respectively. The lower limits of quantification for the six analytes in different tissue homogenates were 0.8-2.2 ng/ml. The validated assay was successfully applied to a tissue distribution study of the six components in rats after intravenous administration of total flavonoids of Scorzonera austriaca Willd; Asteraceae. The results of the tissue distribution study showed that the high concentrations of six components were mainly in the kidney.

Efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs): A meta-analysis of randomized controlled trials

Summary Objective: The aim of this study was to assess the efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs) with meta-analysis method. Method: We included six randomized clinical trials identified from Medline, Embase, Cochrane Library, "ISRCTN Register" and "ClinicalTrials.gov" which compared ceftazidime-avibactam with comparison group. The meta-analysis was performed using Review Manager software version 5.3. Results: Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on microbiological evaluable populations at the test-of-cure visit (95CI 1.10-2.38, p=0.02) and late-follow-up visit (95CI 1.09-2.23, p=0.02) for the treatment of CUTIs. Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on EME populations at the test-of-cure visit (95CI 1.08-4.27, p=0.03) and late-follow-up visit (OR=1.75, 95CI 1.33-2.29, p<0.0001) for the treatment of CUTIs. Similar results were obtained at the late-follow-up visit (OR = 1.58, 95CI 1.26-1.97, p<0.0001) on microbiologically modified intent-to-treat (mMITT) populations for the treatment of CUTIs. We can find better eradication rates for E. coli and Klebsiella pneumoniae based on mMITT populations. In terms of AEs, SAEs and mortality, ceftazidime-avibactam had a safety and tolerability profile broadly similar to the comparison group. Conclusion: This meta-analysis provides evidence of the efficacy of ceftazidime-avibactam as a potential alternative for the treatment of patients with CUTIs, and CIAIs.