Analytical Research and Development, Integrated product development operations, Dr. Reddy's Laboratories Ltd., Bachupally, Qutubullapur, R.R. Dist. 500072, Andhra Pradesh, India.
J Pharm Biomed Anal. 2011 Sep 10;56(2):429-35. doi: 10.1016/j.jpba.2011.05.037. Epub 2011 Jun 6.
A selective and simple reversed phase HPLC method using naphthalethyl stationary phase was developed and validated for the quantitative determination of palonosetron hydrochloride (PALO), its related compounds and degradation products. Chromatographic separation (R(s)>2) was achieved with linear gradient mode of elution at a flow rate of 1 mL/min and with UV detection at 210 nm. The intra and inter-day coefficients of variation were less than 1.0% (RSD). Consistent recoveries were obtained for PALO (99.2-100.5%) and its impurities (90.0-104.8%). All the analytes exhibited excellent linearity with R² value greater than 0.998. Limit of detection (LOD) and limit of quantification (LOQ) were determined to be in the range 0.011-0.013 μg/mL and 0.035-0.046 μg/mL respectively. The test solution was found to be stable up to 5 days. Induced degradation methods were applied to study the degradation behavior of the drug. LC-MS was used to analyze the degraded samples and possible structural identifications were assigned based upon known reactivity of the drug and molecular weights. The m/z values matched with the hydroxylated, keto and N-oxide metabolites of PALO. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.9%.
建立并验证了一种使用萘乙基固定相的选择性和简单反相高效液相色谱法，用于定量测定盐酸帕洛诺司琼（PALO）、其相关化合物和降解产物。采用线性梯度洗脱模式，流速为 1 mL/min，在 210nm 处进行紫外检测，实现了色谱分离（R(s)>2）。日内和日间变异系数均小于 1.0%（RSD）。PALO（99.2-100.5%）及其杂质（90.0-104.8%）的回收率一致。所有分析物均表现出极好的线性，R²值大于 0.998。检测限（LOD）和定量限（LOQ）分别确定为 0.011-0.013μg/mL 和 0.035-0.046μg/mL。测试溶液在 5 天内稳定。采用诱导降解方法研究药物的降解行为。LC-MS 用于分析降解样品，并根据药物的已知反应性和分子量对可能的结构鉴定进行了分配。m/z 值与 PALO 的羟基化、酮化和 N-氧化物代谢物相匹配。对应激样品进行了与合格参比标准品的测定，质量平衡接近 99.9%。
