Simultaneous quantification of arctigenin and its glucuronide conjugate in mouse plasma using ultra-high performance liquid chromatography coupled to tandem mass spectrometry.

Arctigenin is a natural lignin and a main active component of Fructus arctii, the dried fruit of Arctium lappa. This compound was reported to have some biological activities such as anti-inflammatory, antioxidant, antiviral, renoprotective, and antitumor effects. Arctigenin is mainly metabolized to arctigenin-4'-O-glucuronide by UDP-glucuronosyltransferase. In this study, a simultaneous quantification method was established and validated for measuring arctigenin and arctigenin-4'-O-glucuronide in mouse plasma using ultra-high performance liquid chromatography with tandem mass spectrometry. The assay fulfilled the requirements of the United States Food and Drug Administration guideline for assay validation, with a lower limit of quantification of 2.00 ng/mL for arctigenin and 50.0 ng/mL for arctigenin-4'-O-glucuronide. The recovery rate and matrix effect ranged from 78.4 to 102.8% and 92.5 to 106.3%, respectively, for arctigenin, and 74.3 to 109.2% and 94.9 to 110.2% for arctigenin-4'-O-glucuronide. The method was applied to the measurement of plasma concentrations of arctigenin and arctigenin-4'-O-glucuronide in the plasma of mice after administration of arctigenin. All measured concentrations were within the calibration ranges. Our novel method may be useful to measure plasma arctigenin and arctigenin-4'-O-glucuronide concentrations, and contribute to evaluate the pharmacokinetics of arctigenin and arctigenin-4'-O-glucuronide in mice.

Analysis of fall kinematics and injury risks in ground impact in car-pedestrian collisions using impulse.

In vehicle-to-pedestrian collisions, pedestrian injuries occur due to contact with the car and the ground. Previous studies investigated pedestrian kinematic behavior using a parameter study or through statistical analysis although the force interaction between the pedestrian and the vehicle has not been considered. In this study, multibody analyses were conducted for vehicle-pedestrian collisions for adult and child pedestrian with various vehicle shapes. The impulse and impulse moment acting on the pedestrian from the vehicle were introduced, and the kinematic behavior, rotation and ground impact of the pedestrian model were examined. It was found that if an impulse moment acts on the pedestrian when the pedestrian re-contacts with the hood of the car, the angular velocity of the pedestrian's torso changes in the opposite direction (away from the car), and the torso angle prior to the ground contact decreases to less than 90°. This re-contact between the pedestrian and the vehicle was more likely to occur for cases where the collision involves an adult pedestrian, lower hood leading edge (HLE), longer hood length, and lower collision velocity. When the pedestrian torso angle in contact with the ground was less than 90°, the head vertical impact velocity with respect to the ground became less than 2.9 m/s which corresponds to the injury threshold of the head. This study demonstrated that pedestrian-vehicle re-contact is crucial for reducing ground injury. The vehicle shape, pedestrian size, and collision velocity can determine whether re-contact of the pedestrian with the vehicle occurs. This can then explain the factors affecting pedestrian ground impact injury (e.g., higher HLE, higher risk of ground head injury for children) that were shown in previous studies. A strategy to mitigate ground injury is to apply enough impulse moment onto the pedestrian's upper body from the hood in order to change the torso angular velocity during re-contact, thus making the torso angle less than 90°prior to the ground contact.