Determination of Paeoniflorin in Rat Plasma by Ultra-high Performance Liquid Chromatography-Tandem Mass Spectrometry and its Application to a Pharmacokinetic Study.
In this study, a rapid and highly sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was established for the quantification of paeoniflorin in rat plasma. The analyte and the internal standard (IS), hyperoside, were extracted from rat plasma via liquid-liquid extraction with ethyl acetate. LC separation was carried on a Phenomenex Luna C18 column within 2.5 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operated in the multiple reaction monitoring and negative ion modes. The precursor to product ion transitions monitored for paeoniflorin and the IS were m/z 524.8→449.0 and 463.1→300.0, respectively. The assay was validated with a linear range of 0.02~25.6 μg/mL for paeoniflorin. The intra- and inter-day precisions (relative standard deviation%) were within 9.7%, and the recoveries were greater than 65.2%. Paeoniflorin was proven to be stable during all sample storage, preparation and analytical procedures. The method was successfully applied to a pharmacokinetic study of the Baixiangdan Capsule in eight female rats.
Toward a better understanding of metabolic and pharmacokinetic characteristics of low-solubility, low-permeability natural medicines
Abstract Today, it is very challenging to develop new active pharmaceutical ingredients. Developing good preparations of well-recognized natural medicines is certainly a practical and economic strategy. Low-solubility, low-permeability natural medicines (LLNMs) possess valuable advantages such as effectiveness, relative low cost and low toxicity, which is shown by the presence of popular products on the market. Understanding the in vivo metabolic and pharmacokinetic characteristics of LLNMs contributes to overcoming their associated problems, such as low absorption and low bioavailability. In this review, the structure-based metabolic reactions of LLNMs and related enzymatic systems, cellular and bodily pharmacological effects and metabolic influences, drug–drug interactions involved in metabolism and microenvironmental changes, and pharmacokinetics and dose-dependent/linear pharmacokinetic models are comprehensively evaluated. This review suggests that better pharmacological activity and pharmacokinetic behaviors may be achieved by modifying the metabolism through using nanotechnology and nanosystem in combination with the suitable administration route and dosage. It is noteworthy that novel nanosystems, such as triggered-release liposomes, nucleic acid polymer nanosystems and PEGylated dendrimers, in addition to prodrug and intestinal penetration enhancer, demonstrate encouraging performance. Insights into the metabolic and pharmacokinetic characteristics of LLNMs may help pharmacists to identify new LLNM formulations with high bioavailability and amazing efficacy and help physicians carry out LLNM-based precision medicine and individualized therapies. Graphical Abstract
The risk of Listeria monocytogenes infection in beef cattle operations
Aim:  To determine the prevalence of Listeria monocytogenes and associated risk factors among beef operations (cow‐calf and feedlot) in central and southern California.