[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

[LC-MS/MS Determination of Tenofovir in Human Plasma and Its Bioequivalence].

OBJECTIVE: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting tenofovir in human plasma. METHODS: Twenty four healthy male volunteers received a single oral dose of 300 mg tenofovir disoproxil fumarate tablets under fasting and high-fat diet conditions in a randomized four-way crossover bioequivalence study with two preparations of tablets. Plasma samples were taken and analyzed using the LC-MS/MS method. The pharmacokinetic parameters of the two preparations were calculated and compared statistically to evaluate their bioequivalence using Phoenix Winnonlin6.3. RESULTS: Linear detection responses were obtained for tenofovir at the range from 3.13 to 500 ng/mL. The intra- and inter-day precisions were high,with lower than 5.43% [relative standard deviation (RSD)%],high recovery and good stability. The 90% confidence intervals of peak concentration (Cmax) of tenofovir and its area under the curve (AUC0-t and AUC0-∞ ) all fell within the bioequivalence limit 80.00%-125.00% under both fasting and high-fat diet conditions. No significant difference in peak time (Tmax) was demonstrated between the two preparations (P>0.05) . CONCLUSION: The LC-MS/MS method can be used for simultaneous determination of tenofovir in human plasma. The two preparations of tablets are bioequivalent.

[Pharmacokinetics Study of Phentolamine Mesylate Injection in Healthy Volunteers].

OBJECTIVE: To study the pharmacokinetic profile of phentolamine mesylate injection in healthy Chinese volunteers. METHODS: A total of 16 healthy volunteers were randomly divided into two groups, each receiving anterior teeth submucosal infiltration anesthesia and inferior alveolar nerve block anesthesia, respectively. The participants were injected with 0.9 mL, 1.8 mL, and 3.6 mL of 2% lidocaine HCl with 1∶100 000 epinephrine over three periods sequentially, followed by corresponding sequential injection of 0.2 mg, 0.4 mg, 0.8 mg of phentolamine mesylate at the same sites 30 min later.Blood samples were drawn from 5 min before injection to 15 h post the injection of phentolamine mesylate (16 time points). Adverse events were closely observed all the time. Plasma phentolamine mesylate was detected using UPLC-MS/MS with isotope as internal standard. WinNolin 6.1 software was used to calculate the pharmacokinetic parameters. RESULTS: Time to peak concerntration (Tmax) ranged from 12 to 13 min. Half-time of elimination (t1/2) ranged from 3.84 to 4.07 h, with a clearance (CL) of 190 L/h. Peak concentration (Cmax), area under concentration-time curves from 0 to t hour and from 0 to infinite time (AUC0-t and AUC0-∞) increased proportionally in the dose range of 0.2 mg to 0.8 mg. The results of confidence interval analysis showed nearly linear dynamic characteristics for the injection of phentolamine mesylate. All participants experienced mild adverse events, including pain at the injection point, dizziness, and palpitations. These adverse events disappeared without treatments. CONCLUSIONS: Phentolamine mesylate injection is effective for reversing oral local anesthetic effects.