Yinqiaosan is a classic Chinese herbal medicine formula that has been used to treat various bacterial and viral infections by Chinese medicine doctors for over two centuries. In this work, we developed a comprehensive qualitative and quantitative method for identification, quantitation, and quality assessment of chemical constituents of Yinqiaosan formula in four different preparation forms (i.e., decoction, granule, pill, and tablet), which employed ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry with a single exogenous reference internal standard for untargeted metabolomics profiling and global semiquantitative analysis. The use of a single exogenous reference internal standard permitted not only qualitative and quantitative analyses of multiple herbal components in a single instrument run, but also cross-comparison of chemical contents in between all four Yinqiaosan preparation forms. The acquired mass chromatograms were analyzed, quantitated, and compared using multivariate data analysis for similarities and differences of chemical constituents in four Yinqiaosan preparation forms. For the first time, we were able to identify over 100 chemical constituents from each preparation form using the available database. Among the 49 commonly identified compounds in the 4 Yinqiaosan preparation forms, 16 have been reported to have pharmacological activities, which may be used in a network pharmacology study of Yinqiaosan for exploring the underlying mechanism of the herbal formula.
L-asparaginase is used as an effective line of treatment for acute lymphoblastic leukemia and lymphoma, however, the high cost for this treatment restricts the wide-scale clinical application. Genetic engineering technology is used to recombinantly express L-asparaginase, with high yield, which reduced the costs of production, and overall therapy. Despite the effectiveness of this therapy, intravenous injection of L-asparaginase has some side effects, such as allergic reactions, immunosuppression, pancreatitis, neurotoxicity, hepatitis, coagulopathy, and failure to produce antibodies. To overcome this limitation, Nano-delivery systems using nanoparticles as the carrier of L-asparaginase is used as a new type of drug carrier delivery system. It can increase the permeability of biofilms, enhance drug efficacy, reduce drug toxicity, change the distribution of drugs in the body, and improve bioavailability. In this review, we summarized the application of a variety of nano-lipid and polymers as protein recombinant drug carrier systems, and these nano-carrier systems facilitate to increase the blood circulation time, reduce side effects, and improve the biocompatibility of L-asparaginase medicine. The review specifically adds value as there is no article available that has attempted to elevate the emerging Nanodeliverables and their significance in delivering L- sparaginase safely by achieving maximum therapeutic efficacy.
O6‐benzylguanine (O6BG) is an inhibitor of O6‐alkylguanine‐DNA alkyltransferase (AGT). It binds to AGT by transferring its benzyl moiety to the cysteine residue at the active site of the enzyme. O6BG synergizes the cytotoxic effects of alkylating agents by halting AGT‐mediated DNA repair. O6‐benzyl‐8‐oxoguanine (8‐oxo‐O6BG) is a metabolite of O6BG, which is an equally potent inhibitor of AGT. In this work, we report the development and validation of an LC–MS/MS method for simultaneous determination of O6BG and 8‐oxo‐O6BG in human plasma. O6BG and 8‐oxo‐O6BG along with the analog internal standard, pCl‐O6BG, were extracted from alkalinized human plasma by liquid–liquid extraction using ethyl acetate, dried under nitrogen and reconstituted in the mobile phase. Reverse‐phase chromatographic separation was achieved using isocratic elution with a mobile phase containing 80% acetonitrile and 0.05% formic acid in water at a flow rate of 0.600 ml/min. Quantification was performed using multiple‐reaction‐monitoring mode with positive ion‐spray ionization. The linear calibration ranges of the method for O6BG and 8‐oxo‐O6BG were 1.25–250 ng/ml and 5.00–1.00 × 103 ng/ml, respectively, with acceptable assay accuracy, precision, recovery and matrix factor. This method was applied to the measurement of O6BG and 8‐oxo‐O6BG in patient plasma samples from a prior phase I clinical trial.
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