O'Bey K A, Jim L K, Gee J P, Johnson R M
Am J Hosp Pharm. 1982 Jun;39(6):1005-8.
The stability of tobramycin in pooled human serum when combined with ampicillin, carbenicillin disodium, or penicillin G potassium after storage at 0, 23, or 37 degrees C was evaluated. Samples of pooled human serum containing tobramycin sulfate 8 micrograms/ml alone or combined with ampicillin, carbenicillin disodium, or penicillin G potassium 200 micrograms/ml were prepared and stored at 0, 23, and 37 degrees C. Single samples were removed periodically for 48 hours and frozen until assayed. Tobramycin concentration was measured by a radioenzymatic assay. A tobramycin degradation rate constant was calculated for the tobramycin control and each tobramycin-penicillin combination at each temperature; from this, the time for the tobramycin concentration to decline to 90% of the initial concentration (t90) was estimated. Stability of the penicillins was not assessed. Tobramycin degradation approximated a log-linear process in all samples for the 48-hour period. The tobramycin control sample was more stable than any of the tobramycin-penicillin solutions at each temperature. At 0 degrees C, tobramycin mixed with ampicillin was the least stable of all mixtures; at 23 and 37 degrees C, tobramycin mixed with carbenicillin was the least stable. Storing tobramycin and carbenicillin samples on ice (0 degrees C) prolonged t90 from 10 hours (23 degrees C) and 12 hours (37 degrees C) to 36 hours. The t90 values for tobramycin when mixed with ampicillin were 19, 16.5, and 20 hours at 0, 23, and 37 degrees C, respectively. Mixed with penicillin G, tobramycin t90 values at 0, 23, and 37 degrees C were 48, 44, and 16 hours, respectively. More than a 10% loss of tobramycin potency occurred in some tobramycin-penicillin solutions under the conditions of this study. Because this loss would affect the accuracy of tobramycin pharmacokinetic calculations, the authors suggested guidelines for handling tobramycin serum samples.
评估了妥布霉素在与氨苄西林、羧苄西林二钠或青霉素G钾联合使用后，于0、23或37摄氏度储存的混合人血清中的稳定性。制备了单独含有8微克/毫升硫酸妥布霉素或与200微克/毫升氨苄西林、羧苄西林二钠或青霉素G钾联合使用的混合人血清样本，并分别在0、23和37摄氏度下储存。在48小时内定期取出单个样本并冷冻，直至进行检测。通过放射酶法测定妥布霉素浓度。计算了每个温度下妥布霉素对照品以及每种妥布霉素 - 青霉素组合的妥布霉素降解速率常数；据此估算出妥布霉素浓度降至初始浓度90%（t90）所需的时间。未评估青霉素的稳定性。在48小时内，所有样本中的妥布霉素降解均近似呈对数线性过程。在每个温度下，妥布霉素对照样本均比任何妥布霉素 - 青霉素溶液更稳定。在0摄氏度时，与氨苄西林混合的妥布霉素在所有混合物中稳定性最差；在23和37摄氏度时，与羧苄西林混合的妥布霉素稳定性最差。将妥布霉素和羧苄西林样本置于冰上（0摄氏度）储存可使t90从10小时（23摄氏度）和12小时（37摄氏度）延长至36小时。妥布霉素与氨苄西林混合时在0、23和37摄氏度下的t90值分别为19、16.5和20小时。与青霉素G混合时，妥布霉素在0、23和37摄氏度下的t90值分别为48、44和16小时。在本研究条件下某些妥布霉素 - 青霉素溶液中妥布霉素效价损失超过了10%。由于这种损失会影响妥布霉素药代动力学计算的准确性，作者提出了处理妥布霉素血清样本的指导原则。
