| Objective: To study content of the main drugs and theirimpurities injectable piperacillin sodium and tazobactam sodium of three manufacturers and compatible stability with 0.9% sodium chloride injection.Methods: Use HPLC to Determine the content of piperacillin sodium, tazobactam sodium and impurities and Investigate Content changes of piperacillin sodium, tazobactam sodium with 0.9% sodium chloride injection from three manufacturers samples,the chromatographic column was HYPERSIL BDS C18"4.6 mm×250 mm,5μm", the mobile phase was methanol and tetrabutyl ammonium hydroxide (pH3.5 ,50: 50)at a flow-rate of 0.8mL/min, the detection wavelength was 220nm.1. Solution preparation1.1 Preparation for standard solutionsThe piperacillin and tazobactam sodium standards precisely weighed were dispensed by 50% (V/V) methanol aqueous solution respectively, then two stock solution of 16mg/ml for piperacillin sodium and 2mg/ml for tazobactam sodium were prepared respectively1.2 Preparation for Sample solutions for assayingThe piperacillin sodium and tazobactam sodium obtained from Wyeth Pharmaceuticals Co., Ltd., North China Pharmaceutical Group and Zhuhai United Laboratories Co., Ltd were dispensed by 50% (V/V) methanol aqueous solution respectively, then 10mg/ml piperacillin sodium, 1.25mg/ml tazobactam sodium can obtained. 1.3 Preparation for Sample solutions for compatible stability investigation Piperacillin Sodium And Tazobactam Sodium For Injection from the above three manufactures were dispensed by 0.9% sodium chloride respectively, then 10mg/ml piperacillin sodium, 1.25mg/ml tazobactam sodium can obtained.2. Method validation2.1 Selectivity investigationThe standard solution of piperacillin sodium, tazobactam sodium and the mixed solution of above two standard samples were analysed by HPLC respectively, the corresponding chromatograms then obtained.2.2 Calibration investigationThe standard stock solution prepared above was serially diluted with 50% (V / V) methanol solution to standard concentrations of 2,4,8,10,12 and 16mg/mL for piperacillin and 0.25, 0.5,1,1.25,1.5 and 2 mg / ml solution for tazobactam respecively. 1μL of above standard solution was injected into the chromatograph, and the peak area was recorded. According to the peak area and concentration, linear Regression analysis was carried out.2.3 Prescion investigationThe variations and accuracy for prescion study were assessed by integrated peak area attained from the continuous injections of 8mg/ml piperacillin sodium and 1mg/ml tazobactam sodium for 5 times, then the relative standard deviation (RSD) were calculated to assess the prescion of the methods.3. Contents assaying in sample solutionsSample solutions for assaying were injected into the HPLC system with 1μl injection volume, the integrated peak areas were obtained and used for calculating the contents of piperacillin sodium and tazobactam sodium in sample solutions.4. Investigation of compatible stabilityThe sample solution for compatible stability after preparing for 0 h, 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 5.0 h and 6.0 h were injected into the HPLC system, and the peak areas were obtained, then the contents of piperacillin sodium, tazobactam sodium, and the impurities were calculated. At the same time, the appearance changes such as color, turbidity, and precipitation after 6h in room temperature were observed with naked eye.Results1. SelectivityThe retention times of piperacillin sodium and tazobactam sodium were 9.566min and 4.561min, the peaks were well separated, and did not interfere with each other, or with the impurities.2. CalibrationThe standard calibration curve for piperacillin sodium and tazobactam sodium were linear in the concentration ranges of 2~16 mg/ml, and 0.25~2mg/ml, respectively. The correaltion coefficients (R) of piperacillin sodium and tazobactam sodium were 1.0000 and 1.0000, respectively.3. PrecsionThe RSDs of piperacillin sodium and tazobactam sodium were 1.4% and 0.2%, respecitively.4. The contents of piperacillin sodium, tazobactam sodium and impurtitiesThe content of piperacillin sodium in three sample solutions were 102.9%, 96.4% and 103.1%, respecively. The content of tazobactam sodium in three sample solutions were 100.1%, 92.8% and 97.9%, respecively. The content of impurties in three sample solutions were 1.65%, 2.75% and 1.83%, respecively.5. Compatible stablityThere had no color changes, no cloudings, and no precipitations in the sample solutions for comopatible stablity after preparing for 6 h, and the contents of piperacillin sodium, tazobactam sodium, and the impurities were lower than±2%, compared with those prepared at 0 h.ConclusionsThe results showed that the contents of piperacillin sodium, tazobactam sodium and impurities in the products of three manufacturers were in accordance with the related requirements of the Chinese Pharmacopoeia. The products were compatible with 0.9% sodium chloride within 6 h after preparing, supported by the evidences that there had no appearance changes, and the contents of piperacillin sodium and tazobactam sodium were all lower than±2%, which suggested that the piperacillin sodium and tazobactam sodium for injection were compatible with 0.9% sodium chloride. |
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