液相層析法測定含不純物之抗病毒藥物含量   全文下載

Specific and Selective Quantitation of Antiviral Drugs in the Presence of Impurities by Liquid Chromatography

本研究開發且確效一具穩定性指標的逆相高效液相層析法，測定含nevirapine 、lamivudine和 zidovudine等成分之複方抗病毒藥物。以C18層析管柱（250毫米×4.6毫米的ID，5 μm）分離nevirapine 、lamivudine 、 zidovudine和8個不純物thymine 、thymidine 、zidovudine相關複合物B 、 nevirapine相關複合物A 、nevirapine相關複合物B 、水楊酸、cytosine 、 lamivudine對掌異構物。本方法依據ICH指引，就系統適用性、線性、精密度、準確性、再現性、偵測極限、定量極限、選擇性和特異性等進行確效。執行強制降解研究，顯示最佳化的高效液相層析法具穩定性指標能力。過氧化氫會使檢體降解，顯示該類藥物易被氧化。統計分析證明，本方法可以重複且具選擇性，能有效分離檢測藥物及其降解物，因此是一具穩定性指標的方法。本研究也適用於商業產品中抗病毒藥物不穩定性及溶離度測試。

A stability indicating reversed phase high performance liquid chromatography method was developed and validated for the deter-mination of the antiviral drugs of nevirapine, lamivudine and zidovudine in combination drug product. The chromatographic separation of nevirapine, lamivudine, zidovudine and eight specified impurities of thymine, thymidine, zidovudine related compound B, nevirapine related compound A, nevirapine related compound B, salicylic acid, cytosine, lamivudine diastereomer impurity were achieved with Waters symmetry C18 (250 mm × 4.6 mm i.d., 5 µm) column. The method was validated according to the ICH guidelines with respect to system suitability, linearity, precision, accuracy, robustness, LOD, LOQ, selectivity and specificity. Forced degradation study was also performed in tablet to demonstrate the stability indicating power of the optimized HPLC method. The samples were degraded in hydrogen peroxide condition indicating that the drug product is susceptible to oxidation. Statistical analysis proves that the method can be repeated and selec-tive for the estimation of said drugs. The method could effectively separate the drug from its degradation product hence it can be used as a stability indicating method. This developed procedure is also applicable for the determination of instability of the drug and dissolution behaviour of the said products in commercial products.