The stability of cefuroxime sodium (50 mg/mL) in 0.9% sodium chloride injection stored in polypropylene syringes was studied at 25 and 5C by means of a stability-indicating high-performance liquid chromatographic assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation based on five injections was 0.9. There were at least two products of decomposition that separated from the intact drug. The loss in potency was less than 10% after 2 days of storage at 2 5C, and the loss in potency was less than 4% after 21 days of storage at 5 deg C. The pH value increased from 6.9 to 7.3 when the injection was stored at 25 deg C for
2 days, and the pH value increased from 6.9 to 7.0 when the injection was stored at 5 deg C for 21 days. The drug was not adsorbed onto the syringes. The intensity of the lightyellow color increased with the storage period at 25 deg C but did not change significantly with storage at 5 deg C.
Cefuroxime sodium (Figure 1) powder for injection is extensively used to treat many different diseases, such as urinary tract infections and lower respiratory tract infections. Before it is used, it is dissolved in 0.9% sodium chloride injection to a concentration of 50 mg/mL. The resulting admixture is usually filled into 5-mL polypropylene syringes for pediatric use. The manufacturer recommends that the resulting admixture should be used within 24 hours when stored at room temperature and within 7 days when stored at 5 deg C in the refrigerator? Gupta et alz studied the stability of cefuroxime sodium in
0.9% sodium chloride injection and 5% dextrose injection at concentrations of 5 mg/mL and 10 mg/mL. The resulting injections were stored in polyvinyl chloride bags at room temperature and at 5 deg C. The loss in potency was less than 7% after 1 day of storage at 25 deg C and after 30 days of storage at 5 deg C.
The purpose of this investigation was to determine the stability of cefuroxime sodium injection (50 mg/mL) in 0.9% sodium chloride after storage in polypropylene syringes at 25 and 5 deg C and to determine whether the drug was adsorbed onto the syringes.
Materials and Methods
Chemicals and Reagents
All chemicals and reagents were USP/NF or ACS grade and were used without further purification. The cefuroxime sodium powder for injection was form commercial Lot 1ZPO216 (Glaxco Wellcome, Inc., Research Triangle Park, North Carolina).
A high-performance liquid chromatographic (HPLC) system (M-45 pump and model 484 multiple-wavelength detector, Waters Corporation, Milford, Massachusetts) equipped with an injector (Model 7125, Rheodyne, Cotati, California), and a recorder (Omniscribe 5213-12, Houston Instruments, Austin, Texas) were used. A reverse-phase column (catalogue no. 58220U, C^sub 8^, 15 cm, 4.6 mm ID, 5 (mu)m, Supleco Company, Bellefonte, Pennsylvania) was used. All pH values were measured with a Beckman SS-3 Zeromatic pH meter (Beckman Instruments, Fullerton, California).
The mobile phase contained 9.5% (v/v) acetonitrile in water that contained 0.02 M ammonium acetate buffer. The pH of the mobile phase was approximately 6.9. The flow rate was 1.3 mL/minute, the sensitivity was 0.9 AUFS at 274 nm, the chart speed was 30.5 cm/hour, and the temperature was ambient.
Preparation of Injection for Stability Studies Cefuroxime sodium (1.5 g per vial of free base) was used to prepare the injections for the stability study. The powder for injection, which was equivalent to 6 g of cefuroxime, was dissolved in sufficient 0.9% sodium chloride injection (Lot PS 105619, Baxter Healthcare Corporation, Deerfield, Illinois) to bring it to 120 mL (50 mg of cefuroxime per milliliter of injection). The injection was immediately filled into 5-mL polypropylene syringes (catalogue no. 301-603, Becton, Dickinson & Company, Franklin Lake, New Jersey). The syringes were divided into two groups (10 syringes per portion); one group was stored in the refrigerator at 5 +/- 1 deg C, and the other group was stored at 25 +/- 1 deg C. On day zero, the injection was assayed; and the pH value was recorded. The contents of the syringes were assayed again at appropriate intervals, and the pH values were recorded. A 20-mL quantity of injection was also stored at 25 deg C in a 25-mL glass volumetric flask for comparison to determine whether the drug may have adsorbed onto the polypropylene syringes.
Preparation of Standard Solutions
A 105.7-mg quantity of the powder for injection was accurately weighed (105.7 mg is equivalent to 100 mg of cefuroxime free base) and dissolved in sufficient water to make 100 mL of the solution. Those stock solutions were used to prepare solutions of lower concentrations as needed. Because the percent relative standard deviation (RSD) was very good (0.9) as a result of the use of 80 (mu)L for each injection, the internal standard was not used in this study. The most commonly used standard solution of the drug (100 (mu)g/mL) was prepared by diluting 2.5 mL of the stock solution to 25 mL with water.
Preparation of Assay Solutions
A 2.0-mL quantity of the assay solution was diluted to 100 mL with water; 2.5 mL of this solution was further diluted to 25 mL with water.
Decomposition of Cefuroxime Sodium
A 25-mL quantity of the freshly prepared standard solution (100 (mu)g/mL) was boiled in a 150-mL beaker by use of a hot plate. After 90 seconds, it was allowed to cool, the volume was brought to 25 mL with water, and the solution was injected into the chromatograph.
Assay Procedure and the Calculations
An 80-EL quantity of assay solution was injected into the chromatograph under the conditions described. For comparison, a similar volume of the standard solution that contained the same concentration of the drug (based on the label claim) was injected. Because peak heights of the drug were directly related to the concentrations (60 to 110 (mu)g/mL), the results were calculated by use of a simple equation:
(Ph)^sub a^/Ph)^sub s^ x 100 = Percentage of the label claim found where (Ph)^sub a^ is the peak height of drug of the assay solution and (Ph)^sub s^ is the peak height of the standard solution. The results are presented in Table 1.
Results and Discussion
The assay method developed is precise and accurate; the percent RSD is 0.9 (based on five readings). Apparently, the large injection volume (80 )iL) produced accurate and precise results without the use of an internal standard. The concentrations of the drug were directly related to the peak heights (range tested, 60 to 110 (mu)g/mL). It is important that the volume of injection (80 (mu)L) remain constant to ensure a linear relationship between the concentrations and the peak heights. The standard solution, which was decomposed by heat, produced two additional peaks from the products of decomposition (Figure 2C). All products of decomposition eluted before the drug peak. The potency of the intact drug remaining was only 38.5%.
The potency of cefuroxime decreased to 98.1% (Table 1) after 1 day of storage at 25 deg C, and the pH value increased from 6.9 to 7.3. After 2 days' storage at 25 deg C, the potency was 91.5%. After 3 days' storage at 25 deg C, the potency decreased to 87.9%. The pH remained constant (7.3) for 2 and 3 days' storage at 25 deg C. At 25 deg C, a beyond-use date (BUD) of 2 days is the maximum. Since the potency of cefuroxime decreased to
91.5% after storage for 2 days, a 1-day BUD may be more appropriate. At 5 deg C, the loss in potency after 21 days of storage was less than 4%; and the pH value of the injection had increased from 6.9 to 7.0. Therefore, at 5 deg C, a BUD of at least 21 days is appropriate. A 7-day expiration date has been recommended by the manufacturer.1 Obviously, there was no adsorption of drug on the syringes, since the injection that was stored in the glass volumetric flask for 1 day gave results similar to the sample stored in the polypropylene syringes. At 25 deg C, the intensity of the light-yellow color increased with the storage period; and at 5 deg C, there was no significant change in the physical appearance of the injection.
Cefuroxime sodium (50 mg/mL) in 0.9% sodium chloride injection stored in 5-mL polypropylene syringes was stable for 2 days at room temperature and for at least 21 days at 5 deg C.
1. Zinacef [package insert]. Research Triangle Park, NC:Glaxo Wellcome Inc.; 1998:1-2.
2. Gupta VD, Stewart KR. Stability of cefuroxime sodium in some aqueous buffered solutions and intravenous admixtures. J Clin Hosp Pharm 1986;11:47-54.
Vishnu D. Gupta, PhD
Pharmaceutics Division University of Houston Houston, Texas
Address correspondence to: Vishnu D. Gupta, PbD, PhD, Pharmaceutics Division, University of Houston, 1441 Moursund St., Houston, TX 77030. E-mail: firstname.lastname@example.org
Copyright International Journal of Pharmaceutical Compounding Jul/Aug 2003
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