【關鍵詞】 頭孢噻肟；舒巴克坦；色譜法,高壓液相；血漿；尿
【Abstract】 AIM: To establish a determination method of concentrations in human biologic sample following intravenous administration of cefotaxime and sulbactam. METHODS: A RPHPLC method was developed and validated to determine cefotaxime and sulbactam in plasma and urine. The mobile phase of cefotaxime and sulbactam consisted of 1 g/L triethylamine (regulated with phosphate acid to pH=6.2) and methanol in a 68∶32 and 84∶16 (v/v) respectively and pumped at a flow rate of 1 mL/min. The plasma samples were deproteinated by addition of methanol, the urine samples were diluted with super pure water, then 20 μL of supernatant was injected onto a C18 column and monitored with UV detector at 254 nm and 220 nm respectively. RESULTS: The assay of cefotaxime in human plasma and urine were linear over the range of 5.3-530.0 mg/L and 5.45-545.00 mg/L respectively, with the detection limit of 1 mg/L and 0.25 mg/L respectively. The assay of sulbactam in human plasma and urine were linear over the range of 1.04-208.00 mg/L, with the detection limit of 0.50 mg/L and 0.25 mg/L respectively. The average recovery of the method was (89-110)%, and the RSD within and between days were all less than 5%. The cefotaxime and sulbactam sample of plasma and urine stored in a -20℃ refrigerator became stable within 3 d. CONCLUSION: The assay method is rapid, accurate and usable for the determination of cefotaxime and sulbactam concentrations in plasma and urine.
【Keywords】 cefotaxime; sulbactam; chromatography, high pressure liquid; plasma; urine
【摘要】 目的： 為靜滴注射用頭孢噻肟鈉舒巴坦鈉後在血漿和尿液中的藥物濃度分析提供檢測方法. 方法： 採用HPLC測定頭孢噻肟鈉血漿和尿液中濃度. 在血樣中加入甲醇沉澱蛋白後，尿樣用超純水稀釋後取上清液進樣，色譜分析條件: 以C18反相柱作分析柱；柱溫：室溫；流速： 1 mL/min；頭孢噻肟和舒巴坦的流動相分別為：1g/L的三乙胺水溶液（用磷酸調pH值6.2）∶甲醇＝68∶32和84∶16；頭孢噻肟和舒巴坦的`紫外檢測波長分別為254 nm和220 nm. 結果： 頭孢噻肟血樣和尿樣的線性範圍分別為5.3～530.0 mg/L和5.45～545.00 mg/L，最低檢測濃度分別為1.00 mg/L和0.25 mg/L；舒巴坦血樣和尿樣的線性範圍為1.04～208.00 mg/L，最低檢出濃度分別為0.5 mg/L和0.25 mg/L；方法平均提取回收率在 (89～110)%之間；日內、日間RSD均小於5%. 頭孢噻肟和舒巴坦血漿和尿液樣品置於-20℃冰箱3 d內穩定. 結論： 本方法具有快速、簡便、靈敏、準確等特點,適合於頭孢噻肟和舒巴坦血漿和尿液濃度測定.
【關鍵詞】 頭孢噻肟；舒巴克坦；色譜法，高壓液相；血漿；尿
0引言
由湘北威爾曼製藥有限公司開發研製的一類複方新藥注射用頭孢噻肟鈉舒巴坦鈉已經國家食品藥品監督管理局批准進行Ⅰ期臨床試驗（臨床研究批件號：2005L00727）. 頭孢噻肟鈉屬第三代半合成頭孢菌素類，其抗菌譜廣，對革蘭陰性菌、革蘭陽性菌、需氧菌和某些厭氧菌均有較好的抗菌活性，特別對革蘭陰性菌的殺滅作用更強. 隨著頭孢噻肟在臨床的廣泛使用，許多臨床病原菌通過產生β內醯胺酶對頭孢噻肟產生耐藥性而導致臨床治療方案的失敗［1-2］. 舒巴坦為半合成β內醯胺酶抑制劑,與頭孢噻肟合用時出現協同作用，使對頭孢噻肟耐藥的細菌的最低抑菌濃度下降到敏感範圍之內. 為了評價靜滴注射用頭孢噻肟鈉舒巴坦鈉後該藥品在健康志願受試者的耐受性以及藥代動力學特點，我們採用高效液相色譜法測定了生物樣本中頭孢噻肟和舒巴坦的濃度.