Determination of High Molecular Weight Impurities of Cefotiam Hydrochloride for Injection by HPSEC Method / 医药导报

Objective To establish a high performance size esclusion chromatography (HPSEC) method for the determination of high molecular weight impurities of cefotiam hydrochloride for injection.Methods A TSK G2000 SWXL column(7.8 mm × 30 cm,5μm) was used,the mobile phase consisting of phosphate budder solution [0.1 mol·L-1 disodium hyrogen phosphate-0.1 mol·L-1 sodium dihydrogen phosphate (61:39)],the flow rate was 0.7 mL· min-1,the detection wavelength was 254 nm,the column temperature was 30 ℃,the injection volume was 20 μL,and the concentration of polymers was quantified by external standard method.Results For HPSEC method,the calibration curves were linear in the range of 5.0-25.0 μg·mL-1 for cefotiam,and the LOD and LOQ was 0.1 μg·mL-1 and 0.246 μg· mL-1,the RSD for replicate for injections of reference solution was 0.50％,the sample solution was not stable in room temperature.Conclusion The method has high separation efficiency and good specificity,which provides reference for the further study of the polymer of cefotiam hydrochloride for injection.

Determination of Cefotiam in Human Plasma Using Liquid Chromatography-Tandem Mass Spectrometry / 分析化学

In order to evaluate the pharmacokinetic profile of cefotiam hexetil hydrochloride tablet in Chinese healthy volunteers, a sensitive, specific and rapidprotein precipitation-liquid chromatography-tandem mass spectrometry method was developed and validated in human plasma. Chromatographic separation was achieved on a Waters Symmtry-C18 column (50 mm × 4. 6 mm, 5 μm), using a gradient mobile phase consisting of methanol and 1 mmol/ L ammonium acetate in water at a flow rate of 1. 0 mL/ min. Cefotiam and diazepam (internal standard) were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The calibration curve was linear from 5. 0 ng / mL to 5000 ng / mL (r>0. 99) with limit of quantitation of 5. 0 ng / mL. The assay met the published acceptance criteria. This rapid, sensitive and reproducible method was successfully applied to the pharmacokinetic study of cefotiam hexetil hydrochloride tablet in healthy Chinese volunteers and therefore provided a considerable mirror for quantification of other cephalosporins in human matrix.

Determination of Residual Solvents in Raw Material Drug of Cefotiam Hexetil Hydrochloride by Gas Chromatography with Head-space Sampling / 医药导报

Objective To establish a method of gas chromatography with head-space sampling for determination of five residual solvents ( acetone, ethyl acetate, isopropanol, dichloromethane, acetonitrile ) in raw material drug of cefotiam hexetil hydrochloride. Methods Agilent DB-624 capillary column(30 m×0.53 mm,3.0 μm)was used,with FID served as detector and DMF as the solvent. Results Linear relationships were obtained for the 5 residual solvents in their respective concentration ranges ( r=0.999 6-0.999 9,n=5) ,and the detection range was from 0.071 to 0.847μg. The stabilities measured as relative standard deviations ( RSD) for the 5 residual solvents were from 0.40% to 2.12% ( n=3) . The average recovery rates were 99.03% to 103.33%,and RSD were 0.54% to 3.41% ( n=3) . Conclusion The method is simple,sensitive and accurate for the residual solvent analysis in raw material drug of cefotiam hexetil hydrochloride.

Influence of injection cefotiam on vanadate oxidation method and dry chemical method assay total bilirubin / 国际检验医学杂志

Objective Discuss the interference of injection cefotiam on vanadate oxidation method and dry chemical method assay total bilirubin .Methods Collected 60 examples ,include total bilirubin concentration 20 examples less than 20 μmol/L ,20 examples between 150-220 μmol/L and 20 examples between 350-410 μmol/L ,add an equal volume of various concentrations of cefotiam in each case ,formulated into cefotiam final concentrations of 300 ,150 ,75 mg/L of serum samples as the test group ,add an equal volume of water in each serum samples as the control group ,determine all the samples total bilirubin concentration respectively by vanadate oxidation method and dry chemical method ,compared the interference of cefotiam on determined total bilirubin by two method ,analyze the data by SPSS13 .0 .Results Determined total bilirubin by dry chemical method ,the test group higher than the control group ,the difference was statistically significant(P<0 .05) ,at the same total bilirubin levels ,with cefotiam concentrations decreased ,increased rate of total bilirubin concentration were decreased in the experimental group .Determined total bilirubin by vanadate oxidation method ,when the total bilirubin concentration between 150 -220 μmol/L ,the test group was higher than the control group ,the difference was statistically significant(P<0 .05) .Conclusion Interference of injection cefotiam on determined to‐tal bilirubin by dry chemical method is strong ,and with the drug concentration increased ,effect is more obvious ,but determination of total bilirubin by vanadate oxidation method has almost no effect .

Polymer impurities in cefotiam hydrochloride by online 2D-GFC-RPLC-TOFMS / 中国药学杂志

OBJECTIVE: To validate the conventional gel filtration chromatography (GFC) method for determination of the polymer impurities in β-lactam antibiotics and achieve combination of GFC and RP-HPLC system. METHODS: The effectiveness of the conventional GFC method was identified by 2D-GFC X LC-TOFMS and the polymer impurities found by GFC were identified by RPHPLC. RESULTS: The polymer impurities found by GFC mainly were degradation impurities and open β-lactam ring impurities, which could not effectively characterize the sensitizing polymer impurities in cefotiam hydrochloride. CONCLUSION: An effective method to characterize the polymer impurities in β-lactam antibiotics may be established on the basis of online column switching technique which effectively combines the advantages of GFC and the ability of RP-HPLC to identify the special impurities.

Effect of Cefotiam Sodium Combined with Furosemide on Renal Function in Rats / 中国药师

Objective:To evaluate the safety of the combination of cefotiam sodium and furosemide and to provide the reference for clinical medication. Methods:Three groups were established, including the blank control group, cefotiam sodium group at the dosage of 500 mg·kg-1 ·d-1 , cefotiam sodium combined with furosemide group at the respective dosage of 500 mg·kg-1 ·d-1 and 15 mg ·kg-1 ·d-1 . After the continuous administration for 12 days, the renal structure, serum uric acid, creatinine and urea nitrogen, u-rine of α1 microglobulin and β2 microglobulin in the rats were detected. Results:Cefotiam sodium at the dosage of 500 mg·kg-1 · d-1 showed no significant effects on the renal structure, serum uric acid, creatinine and urea nitrogen,urineα1 microglobulin andβ2 microglobulin in the rats. The combination group showed significantly increased urine β2 microglobulin (P<0. 05) and significantly decreased serum uric acid (P<0. 05). Conclusion:Short time use of cefotiam sodium exhibits no significant effect on the renal struc-ture and function in rats, while the combination of cefotiam sodium and furosemide has significant effects on urineβ2 microglobulin and serum uric acid in rats.

A case of cefotiam-contact anaphylaxis / 대한내과학회지

Anaphylaxis caused by beta-lactam antibiotics usually develops following the systemic administration of the drug, although it can also occur with trivial contact of the drug on the skin in extraordinarily sensitive individuals. Cefotiam is a second-generation cephalosporin developed in Japan, and cefotiam-induced contact urticaria and systemic symptoms (contact urticaria syndrome) have been reported in several nurses from Japan and Korea. Considering the serious nature of the systemic manifestations, such as hypotension, contact anaphylaxis is a more appropriate name for severe forms of the disease than contact urticaria syndrome. No previous study has reported a case involving contact urticaria syndrome to multiple drugs. We describe a case of cefotiam-induced contact anaphylactic shock combined with cefoperazone/sulbactam-induced contact urticaria syndrome in a 24-year-old nurse. She exhibited positive skin prick test responses to both cefotiam and cefoperazone/sulbactam.

Comparison Between Cefotiam And Cefotiam / Netilmycin Antibiotic Therapy for Grade III Open Tibial Fractures

We studied the effect of the addition of the bacteriostatic agent, netilmycin, to cefotiam treatment as prophylactic antibiotics against infection for grade III open tibial fractures. From 45 eligible cases, assigned randomly to a control group that receive only cefotiam, and the treatment group that receive netilmycin in addition to cefotiam. We observed that the clearing of infection occurred earlier in the cefotiam /netilmycin group. We found that 3 day administration of cefotiam netilmycin is superior to 3 day administration of cefotiam only. It is equivalent to 5 day treatment with cefotiam alone.

Compatible Stability of Cefotiam Hydrochloride for Injection with Fructose Injection / 中国药房

OBJECTIVE: To investigate the compatible stability of cefotiam hydroloride for injection with fructose injection.METHODS: The content changes of the mixture within 8h at 25℃ were determined by UV spectrophotometry,and its external appearance was observed,and the pH value as well as particle size of the mixture were measured.RESULTS: The mixture was clear within 6h,showing no visible changes in appearance,pH value and contents of cefotiam,with particles in line with the standard stated in China Pharmacopeia(2005 edition).CONCLUSION: The mixture of ceforiam hydrochloride for injection and fructose injection is stable within 6h.

A Case of Cefotiam-Induced Contact Urticaria Syndrome / 대한피부과학회지

Contact urticaria refers to a wheal-and-flare response which occurs on intact skin after application of a chemical. When contact urticaria is accompanied by systemic symptoms, it is known as the contact urticaria syndrome. We report a case of contact urticaria syndrome occurring in a 24-year-old nurse, due to occupational exposure to cefotiam. An open patch test showed a positive reaction to cefotiam.

Occupational Contact Urticaria Syndrome Induced by Cefotiam Dihydrochloride in a Nurse

We herein report a case of occupational contact urticaria syndrome induced by cefotiam di-hydrochloride in a nurse. She had generalized pruritic wheals accompanied by palpitations and tachypnea during the preparation of cefotiam solution. A scratch patch test with cefotiam di-hydrochloride, a major component of cefotiam ingredient showed multiple erythema and wheals within 5 minutes, accompanied by palpitations and tachypnea. No delayed type reaction was observed. Based on her clinical history and scratch test result, we diagnosed her condition as contact urticaria syndrome caused by cefotiam.

A Case of Acute Generalized Exanthematous Pustulosis / 대한피부과학회지

Acute generalized exanthematous pustulosis (AGEP) is initially termed by Beylot to describe a disease entity with sudden onset of amicrobial pustular eruption accompanied with fever and leukocytosis. A 58-year-old man presented with sudden onset of multiple, generally pinhead sized pustules on erythematous base scattered on trunk accompanied with fever. The patient had been on medication of cefotiam prior to skin eruption for 4 days after esophageal cancer operation. Histopathological study of a skin biopsy specimen revealed subcorneal pustules with a few neutrophils and few eosinophils in dermis. After discontinuation of cefotiam and systemic steroid medication for 5 days, the eruption resolved clearly without scars within 4 days.

Two Cases of Cefotiam-induced Contact Urticaria Syndrome

Contact urticaria refers to a wheal-and-flare response after cutaneous exposure to certain chemicals. If contact urticaria is accompanied by systemic symptoms, it is referred to as contact urticaria syndrome. Herein we report two cases of contact urticaria syndrome occur-ring in nurses due to occupational exposure to cefotiam.

A Case of Cefotiam-Induced Contact Urticaria Syndrome / 대한피부과학회지

Contact urticaria refers to a wheal-and-flare response occurring on the application of chemicals to intact skin. When contact urticaria is accompanied by systemic symptoms, it is known as the urticaria syndrome. Fourteen cases of cefotiam-induced contact urticaria have been reported in the foreign literature, but no such case, as far as we know, has been described in the Korean dermatology literature. We report a case of contact urticaria syndrome occurring in a 23-year-old nurse due to occupational contact exposure to cefotiam. She experienced generalized urticaria, itching of the skin, difficulty in breathing, and abdominal pain, when she was preparing an injection of cefotiam. An open patch test showed positive reactions to cefotiam, cefmetazole, and ceftriaxone. Since avoiding cefotiam, the symptoms disappeared and did not recurred.