Objective To establish a reversed-phase HPLC method for determining three stereoisomers in baloxavir marboxil and provide a basis for the quality specification of baloxavir marboxil.Methods The chromatographic column was CHIRALPAK IC-3(4.6 mm × 150 mm,3 μm),The mobile phase was acetonitrile-0.1％formic acid aqueous solution-isopropanol(35:50:15).The column temperature was 40 ℃.The flow rate was 0.5 mL·min-1.The injection volume was 10 μL.The detection wavelength was 259 nm.Result The isomer peaks were completely separated from the principal component peak.The detection limits for stereoisomers 1,2 and 3 were 0.024 7,0.038 7,0.038 1 μg·mL-1 respectively.The quantitation limits for stereoisomers 1,2 and 3 were 0.049 4,0.077 3,0.076 1 μg·mL-1 respectively.There were good linear relationships between the concentrations and peak area within the ranges of the study,and the linearity concentration ranges of stereoisomers 1,2 and 3 were 0.049 5-0.989 0 μg·mL-1,0.051 6-1.031 0 μg·mL-1,0.050 8-1.015 0 μg·mL-1 respectively.The linear correlation coefficients were 0.999 4.The recovery was 92.28％-103.90％.The sample solution was stable in 48 h at room temperature.Conclusion The method is accurate and reliable for determining stereoisomers in baloxavir marboxil,and provide a guideline of quality standards of baloxavir marboxil and safety evalution.

Objective:To investigate the clinical efficacy of Full-endoscopic pars debridement, graft with autograft and recombinant human bone morphogenetic protein 2 (rhBMP-2), and percutaneous pedicle screw (PPS) fixation for the treatment of lumbar spondylolysis.Methods:A retrospective analysis was performed for the case data of 8 patients (7 males and 1 female) of lumbar spondylolysis treated with full-endoscopic pars bone graft with autograft and rhBMP-2 combined with PPS fixation in the fourth medical center of PLA general hospital. The mean age was 21.8±4.1 years (range, 16-29 years). All cases had mono-segmental bilateral pars defects, including 2 cases of L 4 and 6 cases of L 5. The visual analogue scale (VAS) and the Oswestry disability index (ODI) were recorded before and after surgery. MacNab score was used to evaluate the final clinical outcome of lumbar function at 1 year after the removal of internal fixation. Multi-planar reconstruction of CT scans was used to evaluate the bone healing at 6 and 12 months after the operation, and par condition at 1 year after the removal of internal fixation. Pfirrmann's grading system through MRI was used to grade disc degeneration in the fixed and adjacent discs respectively before the operation, before the removal of internal fixation, and 1 year after the removal of internal fixation. Results:All the operations were successfully completed. All patients were followed up for 24-30 months, with an average follow-up time of 27.75±3.11 months. Both VAS of back pain (1.63±0.74, 1.25±0.71、1.00±0.53) and ODI (10.25%±5.17%、6.33%±5.03%、4.86%±3.35%) at 6 and 12 months after the operation and 1 year after the removal of internal fixation were improved compared with those preoperatively (7.25±1.04 and 40.67%±9.67%), with significant differences ( P<0.05). The improvement rates of VAS and ODI at one year after pars repair were 83.31%±8.85% and 85.22%±9.60%, respectively. The improvement rates of VAS and ODI at one year after the removal of internal fixation were 85.96%±6.97% and 88.05%±7.25%, respectively. At the final follow-up, 7 patients had excellent results and 1 patient had good results according to the MacNab criteria. There were 3 patients bony healed in 6 months postoperatively and the remaining 5 patients bony healed in 12 months postoperatively. There was no pars re-rupture at the one-year follow-up after the removal of internal fixation. Disc degeneration increase one grade at the fixed disc in one patient before and after the removal of internal fixation than before pars repair surgery. Disc degeneration increase one grade at the adjacent disc in one patient before and after the removal of internal fixation than before pars repair surgery. There were no intraoperative or postoperative complications, such as nerve injury, cerebrospinal fluid leakage, incision exudation, infection, or breakdown of internal fixation device. Conclusions:Full-endoscopic pars bone debridement, graft with autograft and rhBMP-2, followed by PPS fixation is a safe and effective minimally invasive spine surgery for treating lumbar spondylolysis. It has the advantages of a high fusion rate, low incidence of complications, no pars re-rupture after the removal of internal fixation and no significantly increasing intervertebral disc degeneration in fixed and adjacent discs.

Objective To establish a high-performance liquid chromatography method to detect empagliflozin and related substances in empagliflozin bulk drug and tablets,and to provide technical support for quality control and unified monitoring of empagliflozin bulk drug and its tablets.Methods A liquid chromatography development system with the full factorial design of experiments and the Box-Behnken model was used to screen and optimize the chromatographic parameters.Related substances were detected in empagliflozin API and empagliflozin tablets from different companies with the optimized chromatographic parameters.Results The optimized chromatographic parameters were obtained:Shim-pack GIST C18-AQ column(250 mm×4.6 mm,5 μm)was used,column temperature was 15 ℃,gradient elution with water-acetonitrile as mobile phase was as below,flow rate was 1.2 mL·min-1,detection wavelength was set at 224 nm.The specificity of the method is good,with recoveries ranging from 94.8％to 101.7％,and RSD ranging from 0.5％to 3.1％.The known single impurity in APIs and tablets is less than 0.05％,any other unknown single impurity is less than 0.06％,and the total amount of impurities are less than 0.3％.The related substances of supervised sampling are under good control.Conclusion The method is reliable and robust for determining related substances of empagliflozin and its tablets.

Objective To evaluate the quality of propranolol hydrochloride tablets based on national drug sampling,to analyze existing quality issues and improve their quality standards,to provide references and suggestions for the production,quality control,and supervision of this product.Methods A comprehensive evaluation of 178 batches of sampled products was conducted using legal standards combined with exploratory research,including key quality indicators such as related substances,dissolution,content uniformity,content determination,in vitro dissolution profiles,and genotoxic impurity N-nitrosoproranolol.The quality of domestic propranolol hydrochloride tablets and the controllability of the current quality standards for product quality were assessed.Results According to the legal standard methods,the qualification rate of 178 batches of sampled products was 100%.Exploratory research revealed that the impurity levels of samples from six manufacturing enterprises were far below the limit requirements;however,differences existed in genotoxic impurity N-nitrosoproranolol and other aspects.Conclusions The overall quality of propranolol hydrochloride tablets is good,but the current standards need further improvement.It is recommended to add/revise the detection methods for related substances,content,and content uniformity,strictly control N-nitrosoproranolol,and urge enterprises to pay attention to the quality of excipients and the control of the preparation production process.

Objective To evaluate the quality profile of losartan potassium tablets in China based on national drug sampling and testing,to assess their safety,efficacy,and potential quality risks,and to provide evidence for improving quality standards along with feasible regulatory recommendations.Method A comprehensive evaluation was conducted on 196 sampled batches using statutory standards combined with exploratory studies,including tests for related substances,moisture,nitrites,nitrosamine,and azide genotoxic impurities.Results The compliance rate under statutory standards was 100%.However,exploratory analyses identified variations in moisture and nitrite levels among products,although genotoxic impurities and related substances were either undetectable or well below regulatory limits.Conclusions Losartan potassium tablets demonstrate satisfactory quality,though existing standards require further refinement by adding moisture and nitrite specifications.

Objective To establish a method for the simultaneous determination of peimine,peiminine,and hupehenine in Juhong pills,to investigate the raw material usage of Fritillaria thunbergii Miq.,and to preliminarily develop a detection approach for identifying adulteration with Fritillaria hupehensis Hsiao et K.C.Hsia.Methods The high-performance liquid chromatography-triple quadruple mass spectrometry(HPLC-MS/MS)was performed on an Agilent Poroshell 120 SB C18 column(2.1 mm×100 mm,2.7 μm)with a mobile phase consisting of acetonitrile-methanol(1∶1)and 0.1%formic acid under gradient elution.The flow rate was set at 0.3 mL·min-1.The column temperature was maintained at 35℃,and the injection volume was 2 μL.Electrospray ionization(ESI)in positive ion mode and multiple reaction monitoring were employed to quantify the three components in 170 batches of Juhong pills.Simulated positive samples with varying adulteration ratios of Fritillaria hupehensis Hsiao et K.C.Hsia were prepared to establish a simple yet efficient detection limit for adulteration.Results Three components showed good linear correlation within their ranges(r≥0.997 5),and the averaged recoveries ranged from 92.0%-106.2%.A total of 61 batches were suspected of Fritillaria thunbergii Miq.adulteration with Fritillaria hupehensis Hsiao et K.C.Hsia in raw material inputs,with the peimine to peiminine ratio below 1.15.Among these samples,27 batches were large honey-bound pills with hupehenine levels of 2.636-9.939 μg·g-1;34 batches were water-honeyed pills showing significantly higher hupehenine contamination at 6.752-48.137 μg·g-1.Conclusion The established method is simple,reliable,and accurate for the quality control of Fritillaria thunbergii Miq.adulteration in Juhong pills without imposing significant additional costs.

Objective To systematically evaluate the quality of Fengshiding capsules,to analyze existing problems based on national drug sampling and testing,and to offer references and suggestions for improving quality control and regulatory supervision of this product.Methods A total of 136 batches of Fengshiding capsules were subjected to standard quality tests and exploratory analyses.HPLC was used to establish the content determination of Angelica dahurica,Cynanchum paniculatum,and Glycyrrhizae Radix,as well as the limit test for anabasine in the preparation.Additionally,an UPLC method was also employed to establish the characteristic chromatogram of Fengshiding capsules.A screening method for artificial pigments was developed,and UPLC-MS/MS was used to detect the illegal addition of chemical drugs in Fengshiding capsules.Results All 136 batches of samples passed inspection according to the current quality standards.However,based on exploratory study evaluations,the content determination results of Cynanchum paniculatum,Angelica dahurica,and Glycyrrhiza Radix were below the proposed limits.The limit test for anabasine did not exceed the proposed threshold.Furthermore,the characteristic chromatograms revealed missing peaks in several samples,and some batches contained artificial pigments and residues of acetaminophen.Conclusions The overall quality of Fengshiding capsules is rated as"average"based on national drug sampling and testing.To enhance product quality,it is recommended to improve quality standards,ensure the use of high-quality raw herbal materials,promote stronger internal oversight by manufacturers,and intensify regulatory supervision.

Objective:To investigate the clinical efficacy of Full-endoscopic pars debridement, graft with autograft and recombinant human bone morphogenetic protein 2 (rhBMP-2), and percutaneous pedicle screw (PPS) fixation for the treatment of lumbar spondylolysis.Methods:A retrospective analysis was performed for the case data of 8 patients (7 males and 1 female) of lumbar spondylolysis treated with full-endoscopic pars bone graft with autograft and rhBMP-2 combined with PPS fixation in the fourth medical center of PLA general hospital. The mean age was 21.8±4.1 years (range, 16-29 years). All cases had mono-segmental bilateral pars defects, including 2 cases of L 4 and 6 cases of L 5. The visual analogue scale (VAS) and the Oswestry disability index (ODI) were recorded before and after surgery. MacNab score was used to evaluate the final clinical outcome of lumbar function at 1 year after the removal of internal fixation. Multi-planar reconstruction of CT scans was used to evaluate the bone healing at 6 and 12 months after the operation, and par condition at 1 year after the removal of internal fixation. Pfirrmann's grading system through MRI was used to grade disc degeneration in the fixed and adjacent discs respectively before the operation, before the removal of internal fixation, and 1 year after the removal of internal fixation. Results:All the operations were successfully completed. All patients were followed up for 24-30 months, with an average follow-up time of 27.75±3.11 months. Both VAS of back pain (1.63±0.74, 1.25±0.71、1.00±0.53) and ODI (10.25%±5.17%、6.33%±5.03%、4.86%±3.35%) at 6 and 12 months after the operation and 1 year after the removal of internal fixation were improved compared with those preoperatively (7.25±1.04 and 40.67%±9.67%), with significant differences ( P<0.05). The improvement rates of VAS and ODI at one year after pars repair were 83.31%±8.85% and 85.22%±9.60%, respectively. The improvement rates of VAS and ODI at one year after the removal of internal fixation were 85.96%±6.97% and 88.05%±7.25%, respectively. At the final follow-up, 7 patients had excellent results and 1 patient had good results according to the MacNab criteria. There were 3 patients bony healed in 6 months postoperatively and the remaining 5 patients bony healed in 12 months postoperatively. There was no pars re-rupture at the one-year follow-up after the removal of internal fixation. Disc degeneration increase one grade at the fixed disc in one patient before and after the removal of internal fixation than before pars repair surgery. Disc degeneration increase one grade at the adjacent disc in one patient before and after the removal of internal fixation than before pars repair surgery. There were no intraoperative or postoperative complications, such as nerve injury, cerebrospinal fluid leakage, incision exudation, infection, or breakdown of internal fixation device. Conclusions:Full-endoscopic pars bone debridement, graft with autograft and rhBMP-2, followed by PPS fixation is a safe and effective minimally invasive spine surgery for treating lumbar spondylolysis. It has the advantages of a high fusion rate, low incidence of complications, no pars re-rupture after the removal of internal fixation and no significantly increasing intervertebral disc degeneration in fixed and adjacent discs.

Objective To evaluate the quality of propranolol hydrochloride tablets based on national drug sampling,to analyze existing quality issues and improve their quality standards,to provide references and suggestions for the production,quality control,and supervision of this product.Methods A comprehensive evaluation of 178 batches of sampled products was conducted using legal standards combined with exploratory research,including key quality indicators such as related substances,dissolution,content uniformity,content determination,in vitro dissolution profiles,and genotoxic impurity N-nitrosoproranolol.The quality of domestic propranolol hydrochloride tablets and the controllability of the current quality standards for product quality were assessed.Results According to the legal standard methods,the qualification rate of 178 batches of sampled products was 100%.Exploratory research revealed that the impurity levels of samples from six manufacturing enterprises were far below the limit requirements;however,differences existed in genotoxic impurity N-nitrosoproranolol and other aspects.Conclusions The overall quality of propranolol hydrochloride tablets is good,but the current standards need further improvement.It is recommended to add/revise the detection methods for related substances,content,and content uniformity,strictly control N-nitrosoproranolol,and urge enterprises to pay attention to the quality of excipients and the control of the preparation production process.

Objective To evaluate the quality profile of losartan potassium tablets in China based on national drug sampling and testing,to assess their safety,efficacy,and potential quality risks,and to provide evidence for improving quality standards along with feasible regulatory recommendations.Method A comprehensive evaluation was conducted on 196 sampled batches using statutory standards combined with exploratory studies,including tests for related substances,moisture,nitrites,nitrosamine,and azide genotoxic impurities.Results The compliance rate under statutory standards was 100%.However,exploratory analyses identified variations in moisture and nitrite levels among products,although genotoxic impurities and related substances were either undetectable or well below regulatory limits.Conclusions Losartan potassium tablets demonstrate satisfactory quality,though existing standards require further refinement by adding moisture and nitrite specifications.