采用荧光检测的阿托伐他汀稳定性指示高效液相色谱法测定

Stability-indicating high-performance liquid chromatographic assay of atorvastatin with fluorescence detection.

作者信息

Khedr Alaa

机构信息

King Abdulaziz University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Jeddah, King Saudi Arabia.

出版信息

J AOAC Int. 2007 Nov-Dec;90(6):1547-53.

PMID:18193731

Abstract

The purpose of this work was to develop a sensitive, selective, and validated stability-indicating high-performance liquid chromatographic (LC) assay of atorvastatin (ATV) in bulk drug and tablet form. ATV was subjected to different stress conditions, including UV light, oxidation, acid-base hydrolysis, and temperature. ATV and its degradation products were analyzed on an Agilent Zorbax XDB C18 column using isocratic elution with acetonitrile-0.02 M sodium acetate, pH 4.2 (45 + 55, v/v) for 25 min. The samples were monitored with fluorescence (FL) detection at 282 nm (excitation)/400 nm (emission). The response ratio of FL to UV detection (at 247 nm) for ATV was 1.66. The method showed good resolution of ATV from its decomposition products. The photodegradation products were separated by silica gel thin-layer chromatography using double development with ethyl acetate-n-hexane-glacial acetic acid-methanol (40 + 55 + 0.5 + 4.5, v/v/v/v) followed by (39 + 55 + 0.5 + 5.5, v/v/v/v), and confirmed by LC-FL analysis. The FL response was linear over the investigated range for ATV. The linear range was 10-1200 ng/injection, and the limit of quantitation was 2.0 ng/injection.

摘要

本研究的目的是开发一种灵敏、选择性好且经过验证的稳定性指示高效液相色谱（LC）法，用于测定原料药和片剂形式的阿托伐他汀（ATV）。ATV 分别经受不同的胁迫条件，包括紫外线、氧化、酸碱水解和温度。使用乙腈 - 0.02 M 醋酸钠（pH 4.2，45 + 55，v/v）等度洗脱 25 分钟，在 Agilent Zorbax XDB C18 柱上分析 ATV 及其降解产物。样品通过在 282 nm（激发）/400 nm（发射）处的荧光（FL）检测进行监测。ATV 的 FL 与 UV 检测（在 247 nm 处）的响应比为 1.66。该方法显示出 ATV 与其分解产物之间具有良好的分离度。光降解产物通过硅胶薄层色谱法分离，使用乙酸乙酯 - 正己烷 - 冰醋酸 - 甲醇（40 + 55 + 0.5 + 4.5，v/v/v/v）进行二次展开，随后用（39 + 55 + 0.5 + 5.5，v/v/v/v）展开，并通过 LC - FL 分析进行确认。在所研究的 ATV 范围内，FL 响应呈线性。线性范围为 10 - 1200 ng/进样，定量限为 2.0 ng/进样。