Antibiotics;Residues;Tetracycline;Staphylococcus aureus;Micrococcus luteus Objective To verify the problem that the tetracycline residues test is difficult to carry out in daily work due to the absence of inhibition zone of the positive control solution in the antibiotic residues test(cultivation method) in the section General Chapter 3408 of Chinese Pharmacopoeia(Volume Ⅳ, 2020 edition), and try to put forward solutions.Methods According to the operating steps specified in the tetracycline residues section of General Chapter 3408 of Chinese Pharmacopoeia(Volume Ⅳ, 2020 edition), Micrococcus luteus [CMCC(B) 28001] and Staphylococcus aureus(ATCC 29213) were used as test strains to verify the antibacterial performance of the negative and positive control solution by tube-dish method,respectively.Results Neither the negative control solution nor the positive control solution produced an inhibition zone when Micrococcus luteus [CMCC(B) 28001] was used as the test strain, which leaded to abnormal testing work. The negative control solution had no inhibition zone while the positive control solution exhibited an inhibition zone when Staphylococcus aureus(ATCC 29213) was used as the test strain, which could meet the requirements of method applicability.Conclusion It has been found that Micrococcus luteus [CMCC(B) 28001] cannot be used as an indicator bacterium for the tetracycline residues test in General Chapter 3408 of Chinese Pharmacopoeia(Volume Ⅳ, 2020 edition) through literature review, daily work experience, and multiple experimental verifications, and the fundamental reason for this situation is still unclear. It is recommended to replace the strain with Staphylococcus aureus(ATCC 29213) while keeping other experimental conditions unchanged to ensure successful detection of tetracycline residues.

Objective:To evaluate our self-designed novel guide device for cannulated screwing in the treatment of femoral neck fracture.Methods:Between June 2019 and July 2020, 40 patients with femoral neck fracture were treated with cannulated screwing at Department of Orthopaedics, The Second Hospital Affiliated to Shanxi Medical University. They were divided into a manual group of 20 cases whose cannulated screwing was implemented by hand and a guide group of 20 cases whose cannulated screwing was implemented with the aid of our self-designed guide device. In the guide group, there were 5 males and 15 females, with an age of (48.4±10.2) years (from 18 to 63 years); there were 12 cases of types Ⅰ & Ⅱ and 8 cases of types Ⅲ & Ⅳ by the Garden classification. In the manual group, there were 8 males and 12 females, with an age of (49.8±8.4) years (from 18 to 60 years); there were 13 cases of types Ⅰ & Ⅱ and 7 cases of types Ⅲ & Ⅳ by the Garden classification. All fractures underwent closed reduction and internal fixation with 3 cannulated screws. The intraoperative fluoroscopy, operation time, femoral cortex drilling, angle between the guide pin and the femoral neck axis in the anteroposterior view, angle between the guide pin and the femoral neck axis in the lateral view, fracture healing time, Harris hip score and complications were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). In the guide group, intraoperative fluoroscopy [(10.0±2.2) times], operation time [(41.8±5.6) min], femoral cortex drilling [(4.5±1.1) times], angle between the guide pin and the femoral neck axis in the anteroposterior view (3.0°±0.8°) angle between the guide pin and the femoral neck axis in the lateral view (3.9°±1.0°) and fracture healing time [(6.2±0.5) months] were significantly less or smaller than those in the manual group [(24.8±8.3) times, (60.0±15.3) min, (12.8±2.0) times, 7.2°±1.8°, 7.6°±2.6°, and (7.2±0.5) months] (all P<0.05). There was no significant difference in Harris hip score between the 2 groups ( P>0.05). None of the patients had wound infection, internal fixation displacement, fracture nonunion or screw breakage. Conclusions:Application of our self-designed guide device can shorten operation time, improve accuracy of needle insertion, and reduce drilling attempts in the femoral cortex, making cannulated screwing easier for femoral neck fractures.

In this paper, the uncertainties of correction factors of fluconazole impurities determined by HPLC standard curve method were evaluated, and the main common factors affecting the accuracy of standard curve method were found, so as to improve the accuracy of the method.In this study, the corresponding fitting lines of fluconazole and its impurities A, B, C, D, F and I were established respectively, and the ratio of the slope of fitting lines of each impurity and its corresponding principal component was calculated as the correction factor of the impurity.Then on the basis of GUM method, the uncertainty of each impurity correction factor determined by standard curve method was evaluated according to the established uncertainty evaluation scheme of correction factor determination process.The correction factor and uncertainty of fluconazole impurities A, B, C, D, F and I were 1.068 ± 0.046, 0.102 ± 0.005, 0.0582 ± 0.0031, 1.382 ± 0.121, 0.802 ± 0.067 and 1.383 ± 0.119, respectively, and the coverage factor k was 2.Finally, the contribution rate of each uncertainty component was calculated.In the relative combined standard uncertainties urel(f) of fluconazole impurities A, B, C, D, F and I correction factors, the sum of contribution rate of slope uncertainty urel(K) of the linear equation of principal component and its impurity is more than 85%; in the slope uncertainties urel(K) of linear equation, the contribution rates of uncertainties of solution concentration in 8 of 12 data groups are more than 80%, and the contribution rates of uncertainties introduced by reference substance content in solution concentration are about 80%.It can be seen that the preparation of linear solution concentration is the most influential factor in the determination of impurity correction factor by standard curve method, followed by the linear fitting process.In the preparation process of linear solution concentration, the purity of reference substance is the most influential factor, followed by weighing and pipetting times.The conclusion can help the experimenters to better formulate experimental plans and ensure the accuracy of the results when doing similar work.

To improve the standard of quality control of tazobactam and its preparations in China, national reference standard of tazobactam impurity A was developed. After tazobactam impurity A was synthesized, its structure was validated by infrared (IR), mass spectrometry (MS) and nuclear magnetic resonance (NMR), and its content uniformity and short-term stability were measured and investigated. Then, water content and residue on ignition of impurity A were determined, and its purity was determined using high performance liquid chromatography (HPLC) with 10 mmol/L ammonium acetate solution-acetonitrile (98∶2) as the mobile phase. Mass balance method was used to determine the content of the first batch of tazobactam impurity A national standard substance. Meanwhile, nuclear magnetic quantitative method was used to calculate the content, which was mutually verified with the mass balance method. The developed reference material of tazobactam impurity A is consistent with the maximum degradation impurity in tazobactam system applicability solution and the reference material of tazobactam related substance A contained in USP41. Within the 95% confidence range, the ratio of inter- and intra-bottle variance of impurity A after separation was 0.61 (< F0.05(11,12)), proving that the uniformity was satisfying. The contents of organic impurity, water content and inorganic impurity in impurity A were 0.90%, 1.24% and 0.25%, respectively. The content of impurity A was determined to be 97.6% by mass balance method, which was basically consistent with the result of nuclear magnetic quantitative method (97.1%). Under the condition of 25 °C, the area normalized purity of impurity A was 99.1% at 0, 3, 5 and 10 days, proving that the sample was stable at room temperature for 10 days. Finally the first batch of national standard substance of tazobactam impurity A was established successfully.