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别嘌醇与五种抗肿瘤药物混悬液的稳定性

Stability of allopurinol and of five antineoplastics in suspension.

作者信息

Dressman J B, Poust R I

出版信息

Am J Hosp Pharm. 1983 Apr;40(4):616-8.

PMID:6846371
Abstract

The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.

摘要

研究了别嘌醇、硫唑嘌呤、苯丁酸氮芥、美法仑、巯嘌呤和硫鸟嘌呤各自在临时配制混悬液中的稳定性。将每种药物的片剂碾碎,与助悬剂混合,并用单糖浆和野樱桃糖浆按2:1的混合物定容至10、15或20 ml。配制的混悬液浓度如下:别嘌醇(20 mg/ml)、硫唑嘌呤(50 mg/ml)、苯丁酸氮芥(2 mg/ml)、美法仑(2 mg/ml)、巯嘌呤(50 mg/ml)和硫鸟嘌呤(40 mg/ml)。使用高效液相色谱法或紫外扫描,在室温或5℃下储存长达84天的期间,定期对每种混悬液进行双份测定。混悬液降至标示浓度的90%以下所需的时间用作药物稳定性的指标。别嘌醇和硫唑嘌呤在室温及5℃下至少稳定56天。苯丁酸氮芥在室温下迅速分解,但在5℃储存时稳定7天。美法仑混悬液即使在初始测定时也不符合规定的稳定性标准。巯嘌呤和硫鸟嘌呤在室温下分别稳定14天和84天;在5℃时,测定值低于在室温下获得的值。在所测试的混悬液制剂中,别嘌醇、硫唑嘌呤、巯嘌呤和硫鸟嘌呤在室温下至少稳定14天;苯丁酸氮芥混悬液应冷藏并在7天后丢弃。美法仑分解太快,使得这种混悬液制剂无法用于临时调配。

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