An HPLC method for the determination of 18alpha-glycyrrhetinic acid and 18beta-glycyrrhetinic acid in rat plasma was established, which was used subsequently to determine the pharmacokinetic profiles of both epimers of glycyrrhetinic acid in rats. alpha-glycyrrhetinic acid, beta-glycyrrhetinic acid, and a mixture of alpha-glycyrrhetinic and beta-glycyrrhetinic acids were administered to rats via gastric infusion. Blood samples were collected at different time intervals and extracted by liquid-liquid extraction. Separation was achieved by using a Kromasil C18 column (150 mm x 4.6 mm, 5 microm) with the mobile phase composed of acetonitrile--4 mmol x L(-1) ammonium acetate solution (46 : 54, v/v) at a flow rate of 1.0 mL x min(-1), and the detection wavelength was set at 250 nm. The pharmacokinetic parameters were calculated using the software DAS 2.0. In a combined administration, the main pharmacokinetic parameters of beta-glycyrrhetinic acid are significantly different from that of alpha-glycyrrhetinic acid (P < 0.05), while no significant difference was obtained when administrated individually. Compared to the single administration, significant differences (P < 0.05) on the values of AUC(0-t) and AUC(0-infinity) of beta-glycyrrhetinic acid were observed when this chemical was administrated together with alpha-glycyrrhetinic acid. In contrast, the pharmacokinetic parameters of alpha-glycyrrhetinic acid were not affected even under the co-administration. Here, a sensitive, specific, rapid and reproducible HPLC method was developed for the pharmacokinetic studies of alpha-glycyrrhetinic acid and beta-glycyrrhetinic acid in rat plasma.

BACKGROUND:Total knee arthroplasty is an effective treatment for late-stage osteoarthritis,but postoperative pain and joint function recovery are the main challenges.Nerve block and mixed drug injection are two common pain relief methods,but the effect of their combined use is still unclear. OBJECTIVE:To investigate the effects of ultrasound-guided continuous adductor canal block+single sciatic nerve block+"cocktail"mixed drug analgesia on postoperative pain relief and joint function recovery in total knee arthroplasty. METHODS:120 patients with osteoarthritis admitted to Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine from January to May 2022 were randomly divided into two groups(n=60).The observation group received ultrasound-guided continuous adductor canal block+single sciatic nerve block+"cocktail"mixed drug analgesia.The control group received ultrasound-guided continuous adductor canal block+single sciatic nerve block.The differences in visual analog scale score,hospital for special surgery score,pain mediators,expression levels of inflammatory factors,the occurrence of adverse reactions,and postoperative barehanded muscle strength test were compared between the two groups. RESULTS AND CONCLUSION:(1)The visual analog scale scores at rest and exercise were lower in the observation group than those in the control group at 6,8,12,24,48,and 72 hours postoperatively(P<0.05).(2)Hospital for special surgery scores at 1 and 3 months postoperatively were significantly higher in the observation group than those in the control group(P<0.05).(3)In terms of pain mediators and inflammatory factors,the expression levels were significantly lower in the observation group than those in the control group(P<0.05).(4)There was no statistically significant difference in terms of adverse effects and postoperative barehanded muscle strength examination between the two groups(P>0.05).(5)In total knee arthroplasty,ultrasound-guided continuous adductor canal block and single sciatic nerve block,together with a"cocktail"mixed drug analgesia injected into the joint cavity,can provide excellent analgesia,facilitate the recovery of joint function,and relieve postoperative pain and inflammation with a high degree of safety.