利用序列注入分析技術及化學計量優化法開發diltiazem分析方法   全文下載

Employing Sequential Injection Analysis Technique and Chemometric Optimization Approach for Developing Diltiazem Assay Method

序列注入分析技術（SIA）以及化學計量優化法首次被應用於研發分析diltiazem製劑方法，本試驗以分光光度儀（波長526 nm），檢測酸性介質中diltiazem的高錳酸鹽減少量，利用二立方全因子實驗設計和反應曲面圖（response surface plot）求得最佳之高錳酸鹽濃度、強酸性介質濃度以及流速，本方法依據國際純化學與應用化學聯合會（IUPAC）之準則確效，比爾吸收定律範圍內（10-180 mg/L），獲良好線性關係（相關係數 = 0.9996）及回收率（95.4-98.1%）。實驗結果顯示具良好重複性（RSD = 1.19-1.64%，n = 10）及中間精密度（2.84%，n = 5，每天一次），其敏感度亦足以檢測diltiazem製劑，偵測極限和定量極限分別為1.30 mg/L和3.94 mg/L，且檢體處理快速，一小時可達32件。本試驗除使用製劑做為檢體，並以另一已經確效的方法，平行分析比對結果。總而言之，此結合序列注入分析技術（SIA）以及化學計量優化法之新方法，準確、精密，敏感且快速，由儀器設備和試劑消耗的觀點來看，也很經濟，不但溶劑處理安全，並可顯著節省耗材及人力，相當適合應用於藥物實驗室品質控管。

Sequential injection analysis (SIA) technique and chemometric optimization were employed, for the first time, to develop a new method for the assay of diltiazem in pharmaceutical formulations. The method was based on the spectrophotometric detection of permanganate reduction by diltiazem in acidic media at 526 nm. The 23 full factorial design and response surface plot were adopted to optimize permanganate concentration, acid concentration and flow rate. The method was validated as per the International Union of Pure and Applied Chemistry (IUPAC) guidelines. Relatively, wide Beer’s law limit (10-180 mg/L) with satisfactory linearity (correlation coefficient = 0.9996) and recovery (95.4-98.1%) were obtained. The method also recorded good repeatability (RSD = 1.19-1.64%, n = 10) and intermediate-precision (2.84%, n = 5, once per a day). The method is sensitive enough for determining diltiazem in pharmaceutical formulations with limits of detection (1.30 mg/L) and quantification (3.94 mg/L). The method is rapid with sample frequency of 32 sample/h. The method was applied to real pharmaceutical samples and the results obtained were realized by parallel analysis by another validated method. The method enjoys the potentials of SIA and chemometric optimization with respect to good accuracy, precision, sensitivity and rapidity. The method is also inexpensive in terms of instrumentation as well as the consumption of reagents and samples. Besides good safety for handling solutions, the SIA technique offers significant waste minimization and manpower reduction to the proposed method. Therefore, the SIA method is suitable in pharmaceutical laboratory for quality control purpose.