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OBJECTIVE To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR） caused by cefotaxime sodium in Shandong province， and to explore the effects of skin test before medication of cefotaxime sodium on serious ADR， so as to provide reference for safe drug use in clinic. METHODS The relevant data of cefotaxime sodium-induced ADR reported by Shandong Province ADR Monitoring Center during December 2019 to December 2021 were collected from National ADR Monitoring System. The ADR classification， age， gender， ADR occurrence time， route of administration， history of allergy， primary diseases， ADR systems/organs involved， clinical manifestations， outcome， skin test or not before medication were statistically analyzed. RESULTS A total of 1 057 ADR reports caused by cefotaxime sodium were included. Among them， there were 867 patients （82.02%） with general ADR and 190 patients （17.98%） with serious ADR. The majority were ＜11 years old （40.30%）. The main route of administration was intravenous drip （96.69%）. A total of 1 033 patients （97.73%） developed ADR 30 min to 24 h after medication. A total of 814 patients （77.01%） had no history of allergy. The primary diseases were respiratory system infection （56.58%）. Main systems/organs involved in ADR were skin and its appendants， digestive system and respiratory system， and its clinical manifestations were rash， pruritus， nausea， vomiting， chest tightness， etc. After withdrawal or symptomatic treatment， 1 050 patients （99.34%） were cured or improved. Before the use of cefotaxime sodium， 850 patients underwent skin test （151 patients occurred serious ADR）； there was no statistical significance in the incidence of serious renzhen202102@163.com ADR， compared with the incidence of serious ADR in 207 patients without skin test （39 patients occurred serious ADR）（P＝0.718）. CONCLUSIONS ADR caused by cefotaxime sodium is mainly seen in patients ＜11 years old， mostly occurring 30 min to 24 h after intravenous drip； skin test before medication of cefotaxime sodium cannot reduce the risk of serious ADR. Before using cefotaxime sodium in clinical practice， patients should be asked about their allergy and medication history in detail. During use， it is important to focus on the patient’s condition within 24 h after medication to prevent serious ADR and ensure the safety of clinical medication.
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The joint application of traditional Chinese medicine injection containing chlorogenic acid (CA) and cefotaxime sodium (CS) is sometimes appeared in clinical practice, but the scientific basis of drug molecular compatibility is still weak. This study proposes a sequential analysis strategy based on isothermal titration calorimetry (ITC), cold-spray ionization mass spectrometry (CSI-MS) and antibacterial activity test to evaluate the molecular interactions between CA and CS. The results of ITC experiments showed that the Gibbs free energy ΔG < 0 and it was driven by enthalpy change when CA titrated CS, suggesting CA could spontaneously chemically react with CS. Subsequently, the parent ions (m/z 808.143 5) of binding molecular of CA and CS was detected by CSI-MS, indicating CA could chemically bond with CS. Furtherly, the antibacterial experiments found the antibacterial ability of CS against Klebsiella pneumonia was significantly reduced (P < 0.01) by CA in mixed solution. Finally, molecular docking technology showed CA and CS have a common target of penicillin binding protein 3 (PBP3), suggesting that the phenomenon of CA reduced the antibacterial ability of CS may be related to the competitive binding of two components with PBP3. Our studies have shown that CA could spontaneously chemically bond to CS and reduced its antibacterial ability, providing scientific data for molecular interaction evaluation of CA and CS.
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OBJECTIVE: To establish a high performance size exclusion chromatography(HPSEC) method for the separation and analysis of polymers in cefotaxime sodium and cefotaxime sodium for injection, and determine the structures of the impurities by LCMS. METHODS: HPSEC was performed by using Sepax SRT SEC-150(7.8 mm × 300 mm, 5 μm) column. The mobile phase was 0.1 mol•L-1 disodium hydrogen phosphate and 0.1 mol•L-1 phosphate buffer solution. The flow rate was 0.8 mL•min-1, the detection wavelength was set at 235 nm, the injection volume was 10 μL, and the column temperature was maintained at 35 ℃. The concentration of polymers was quantified by external standard method. The LC-MS/MSn system conditions were as following: the mobile phase was 20 mmol•L-1 amonium acetate, the flow rate was 0.8 mL•min-1, ESI source with positive and negative ion scan was utilized, the scanning range was m/z 200 - 1 600, and the post-column diversion ratio was 1:4. RESULTS: Eight impurity peaks were obtained in total; the resolutions were all greater than 1. 5. The linear range of cefotaxime was 1 - 100 μg•mL-1 (r = 1.000 0). The RSD repeatability was 1.2%(n = 6). The limit of detection was 0.2 μg and the limit of quantitation was 0.4 μg. Three polymers were identified by LC-MS. CONCLUSION: The HPSEC method can be used for the quantitative and qualitative analyses of individual polymer impurities. It is also sensitive for the control of polymers in cefotaxime.
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Objective To investigate the clinical efficacy of piperacillin/tazobactam in the treatment of community acquired pneumonia (CAP).Methods 100 cases of CAP in Songyang People's Hospital from March 2016 to March 2017 were collected and randomly divided into two groups according to the digital table , with 50 cases in each group .The piperacillin/tazobactam group was treated with piperacillin/tazobactam , and the cefotaxime sodium group was given cefotaxime sodium .The clinical indicators ,symptoms and imaging effects ,blood indicators ,blood gas analysis and inflammatory indicators were compared between the two groups .Results The clinical symptoms disap-peared time,hospitalization time and hospitalization expenses in the piperacillin /tazobactam group were (3.77 ± 1.12)d,(8.44 ±2.47) d,(1780 ±489) CNY,respectively,which were significantly lower than those in the cefotaxime sodium group [(5.36 ±1.70)d,(11.37 ±3.68)d,(2136 ±470)CNY,t=5.523,4.675,3.711,all P<0.01].The effective rate of the piperacillin/tazobactam group was 90％,which was significantly higher than 70％ of the cefotaxime sodium group (χ2 =6.25,P <0.05).The effective rate of imaging treatment in the piperacillin /tazobactam group was 94％,which was significantly higher than 68％in the cefotaxime sodium group (χ2 =10.981, P<0.01).After treatment,the WBC and neutrophil percentage of the piperacillin/tazobactam group were (7.30 ± 1.08) ×109/L,(0.65 ±0.04),respectively,which were significantly lower than those of the cefotaxime sodium group [(8.66 ±1.25) ×109/L,(0.71 ±0.04),t=5.821,7.405,all P<0.01].The PaO2 level of the piperacillin/tazobactam group was significantly higher than that of the cefotaxime sodium group [(81.90 ±6.83)％vs.(74.20 ± 6.27)％,t=5.873,P<0.01].The levels of CRP,PCT,IL-1 and TNF-αin the piperacillin/tazobactam group
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OBJECTIVE:To optimize the solution preparation in related substance test of cefotaxime sodium.METHODS:HPLC method was adopted to determine the total amount of impurities in cefotaxime sodium.Using phosphoric acid buffer solution pH,placing temperature,standing time and illumination as factor,the total amount of impurities as indexes,the preparation condition of solution was optimized by L9(34) orthogonal test.The validation test was carried out.RESULTS:The optimal preparation method was as follows as the sample was dissolved with a solvent containing pH 6.50 phosphate buffer protected from light.The test temperature and the sample temperature were set at 5 ℃,and the sample was injected within 5 min after the preparation of the solution.CONCLUSIONS:The optimized method is reproducible and reliable.
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OBJECTIVE: To establish an HPLC-MS method for the analysis of the impurity profile of cefotaxime sodium. METHODS: Shimadzu-LCMS-IT-TOF was used with Waters XBridge Shield (RP18, 4.6 mm×250 mm, 5 μm) column. Mobile phase A was 20 mmol·L-1 ammonium acetate (pH adjusted to 6.25)-methanol (92: 8), and mobile phase B was set at 20 mmol·L-1 ammonium acetate-methanol (60: 40) (pH adjusted to 6.25).Gradient elution was performed at a flow rate of 1.0 mL·min-1. ESI source was used.Positive and negative ion scanning was conducted in the range of m/z 150-900.The heating temperature was 200℃, CDL temperature was maintained at 200℃, atomization gas flow rate was 1.5 L·min-1, dry gas pressure was 94.0 kPa, and the post-column diversion ratio was 1: 4.Some related substances in cefotaxime sodium were identified by comparing the retention time in chromatography, [M+H]+ spectrum and MS2 spectrum with those of reference substances, the others which haven't reference substances were deduced or speculated by analyzing the MS2 or MSn fragmentation with the help of a rule summarized from the MS2 fragmentation of cefotaxime sodium and the reference substances of system suitability impurities. RESULTS: Twenty-six related substances were separated and detected in the sample, all of which were identified or deduced. They were cefotaxime sodium isomeric compounds and homologs generated during the production process or degradation products. CONCLUSION: The method can be applied in the identification and qualitative analysis of the related substances of cefotaxime sodium and the quality control and optimization of the synthesis of cefotaxime sodium.
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OBJECTIVE:To establish a method for the content determination of polymer in Cefotaxime sodium and tazobactam sodium(6∶1)for injection. METHODS:High performance size exclusion chromatography(HPSEC)was performed on the column of TSK-GEL G2000SWXL with mobile phase of 0.01 mol/L phosphate buffer (pH 7.0) at a flow rate of 1.0 ml/min,detection wavelength was 254 nm,injection volume was 10 μl and the column temperature was 25 ℃. RESULTS:Cefotaxime and the poly-mers were well-separated;the linear range of cefotaxime was 2.3-226.4 ng(r=0.999 9);RSDs of precision and reproducibility tests were no more than 0.79%;results of durability test showed the changes of column temperature,flow rate,wavelength,pH and mobile phase salt concentration had little effects on the separation among different polymer peaks and between polymer peaks and main peaks. CONCLUSIONS:The method is simple,specific and sensitive,and can be used for the content determination of poly-mer in Cefotaxime sodium and tazobactam sodium(6∶1)for injuction.
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OBJECTIVE:To study the bacterial endotoxin test for cefotaxime sodium injection METHODS:Detection was carried out according to the principle and procedure in Chinese Pharmacopeia,2000 edition RESULTS:Cefotaxime did not interfere with limulus agent in maximal effective diluted concentration CONCLUSION:Bacterial endotoxin test could be used to replace the pyrogen test which is set in departmental standard
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0.05),however,the average cost in combined group was significantly lower than in single group(P
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0.1) except for a concentration reduction by more than 10% in 5% glucose injection in PVC infusion packages at 25℃.CONCLUSION:5% glucose injections in PVC infusion packages should not be used under high temperatures in the clinic.