丁基原啡因穿皮貼片劑之安定性指標液相層析法的開發與確效   全文下載

Development and Validation of a Stability Indicating HPLC Method for the Determination of Buprenorphine in Transdermal Patch

某一快速且敏感的安定指標液相層析法已開發且確效完成，用以測定丁基原啡因穿皮貼片劑中的含量。層析條件如下：以XBridgeTM Shield RP18為層析管柱；移動相為乙?/0.063 M 碳酸氫銨緩衝液（pH 9.5）（58:42, v/v）；流速為1.5 mL/min；偵測波長為230 nm。系統適用性的結果顯示，丁基原啡因與其不純物可完全分離。對丁基原啡因進行中性、酸性與鹼性水解和化學氧化試驗，以評估其專一性。其檢量線的範圍為30~70 μg/mL，且呈現良好線性關係（r = 0.9999, n = 5）。同日與異日精密度之相對標準偏差的範圍分別為0.04 到0.22% 與0.65 到0.88% 之間。回收率平均值範圍從98.86 到 99.36% 之間。偵測極限與定量極限分別為0.008 與0.024 μg/mL。此方法的耐變性是評估移動相中的pH、移動相（組成之）比例與流速等小變動是否造成影響。安定性研究的結果顯示，丁基原啡因於酸性和鹼性環境下之水解反應遵循零級動力學模式，且在過氧化氫的環境下遵循一級動力學模式。此分析方法可成功地用於測定丁基原啡因穿皮貼片劑中的含量，且亦可用於日常例行的品管分析。"

A rapid and sensitive stability indicating HPLC method has been developed and validated for the determination of buprenorphine (BPN) in transdermal patch. Chromatographic separation was achieved isocratically on an XBridgeTM Shield RP18 column with a mobile phase of acetonitrile / 0.063 M ammonium bicarbonate buffer (pH 9.5) (58:42, v/v) at the flow rate of 1.5 mL/min with UV absorbance monitoring at 230 nm. The system performance was evaluated and the result showed that BPN and degradation products were separated. Buprenorphine was subjected to neutral, acidic and basic hydrolysis as well as chemical oxidation to evaluate the specificity. The calibration curve of buprenorphine was linear in the range of 30~70 μg/mL (r = 0.9999, n = 5). The values of RSD (%) for the intra-day and inter-day precision ranged from 0.04 to 0.22 and 0.65 to 0.88%, respectively. The average of the recovery percentage ranged from 98.86 to 99.36%. The detection limit (DL) and quantitation limit (QL) for buprenorphine were 0.008 and 0.024 μg/mL, separately. The robustness of this method was also evaluated on the small fluctuations of pH in the mobile phase, the mobile phase compositions, and the flow rate. The results of stability studies showed the hydrolysis reaction of buprenorphine followed zero-order kinetics model in acidic and basic environment and followed first-order kinetics model in the presence of hydrogen peroxide. This analytical method was successfully applied to the determination of buprenorphine in transdermal patch and can be used for routine quality control work.