應用HPLC方法測定Dicloxacillin原料藥及其製劑之力價

Determination of Dicloxacillin Preparations by High Performance Liquid Chromatography

范燕珍(Yann-Jen Fann) ； 許美智(Mei-Chich Hsu)

《藥物食品檢驗局調查研究年報》 9號 (1991/09) Pp. 128-135

https://doi.org/10.6946/ASRNL.199109.0128

摘要

本研究發展出一種高效液相層析法，可用於鑑別及測定Dicloxacillin之原料藥及其膠囊製劑之力價，簡單、迅捷且具特異性。使用μ-BondapakC18為層析管，以甲醇與4%醋酸(60:40)之混合液為移動相，dimethylphthalate為內部標準品，於254nm波長處以紫外光偵測器測之。標準向線(Standard Curve)之線性回歸方程式為Y=0.0235+0.0197X，相關係r＝0.9999（濃度範圍為0.2~3.0mg/ml）。模擬市售Dicloxacillin 250mg及125mg膠囊處方，所得之平均回收率分別為99.77%及99.60%。重覆注射同一濃度之Dicloxacillin標準品溶液，所測得之變異係數(C.V.)為0.24%，顯示本法再現性(Reproducibility)極高。
為得知HPLC法是否可取代微生物法測定Dicloxacillin製劑之力價，Dicloxacillin各製劑同時以二種方法作配對實驗測定力價，並用paired-t test作配對比較，結果發現，於99%可信度範圍(confidence level)內，原料藥，250mg及125mg膠囊各同時以二種方法測定所得之力價並不具統計上之差異。亦即HPLC法可用以取代微生物法測定Dicloxacillin各製劑之力價。而且各製劑及其熱分解檢品以二種方法測定所得結果之線性關係亦將於本文中討論。

並列摘要

A reverse-phase liquid chromatographic (RP-LC) method was developed for the assay of dicloxacillin in bulk drug and pharmaceutical preparations. The samples were analyzed on a μ-Bondapak (C18) column with a mobile phase of methanol-4% acetic acid (60:40) at a flow-rate of 1.5ml/mm and UV absorbance detection at 254nm. Equations were presented for linear relationships between peak area ratios of dicloxacillin to dimethylphthalate (internal standard) and the dicloxacillin concentration over a range of 0.2-30mg/ml (r=0:9999). Standard addition recoveries were generally greater than 98.4% with all dosage forms. The coefficient of variation was less than 0.24%.
Furthermore, dicloxacillin formulations were assay by microbiological and RP-LC methods to determine whether the RP-LC analytical method is a suitable substitute for the microbiological method. Paired assay results by the two analytical methods were obtained from capsule, formulations containing dicloxacillin and degraded dicloxacillin. Statistical tests were used to assess the equivalence of the paired assay results. The data showed there was no statistically significant difference in mean potency of dicloxacillin bulk drug and pharmaceutical preparations when compared the results obtained from the two methods. The results indicated that the RP-LC method is a suitable substitute for the microbiological method for potency assays and stability studies of dicloxacillin formulations.