用于注射用培美曲塞二钠（抗肿瘤药）中有关物质的生态友好型稳定性指示 HPLC 方法。

Eco-Friendly Stability-Indicating HPLC Method for Related Compounds in Pemetrexed Ditromethamine (Antineoplastic Agent) for Injection.

机构信息

Vignan's Foundation for Science, Technology and Research University (VFSTR), Department of Chemistry, School of Applied Science & Humanities, Vadlamudi, Guntur District, Andhra Pradesh 522213, India.

Ascent Pharmaceuticals Inc., Quality Control, Central Islip, NY 11722, USA.

出版信息

J AOAC Int. 2024 May 2;107(3):415-429. doi: 10.1093/jaoacint/qsae008.

DOI:10.1093/jaoacint/qsae008

PMID:38310337

Abstract

BACKGROUND

An eco-friendly analytical technique was developed with the intention of preserving the environment by using green chemistry principles. Pemetrexed is a folate analogue indicated for the treatment of advanced lung cancer.

OBJECTIVE

Development of a green stability-indicating HPLC method for the quantification of pemetrexed ditromethamine (PDT) impurities in Active Pharmaceutical Ingredient (API) and parenteral dosage form.

METHODS

Chromatographic separation was achieved using a Zorbax SB C18 column (150 mm × 4.6 mm i.d., 3.5 µ particle size) with perchlorate buffer (pH 3.0 ± 0.1, 50 mM) as mobile phase A and acetonitrile-perchlorate (90 + 10, v/v) buffer as mobile phase B at a flow rate of 0.8 mL/min with a column temperature of 40°C ± 0.5°C. All analytes were well resolved by gradient elution with a total run time of 75 min. The UV detection wavelength was 230 nm.

RESULTS

The RP-HPLC method is capable of resolving all the degradation and process impurities for PDT API and parenteral dosage form. The related compounds method was validated in accordance with International conference on harmonization (ICH) Q2(R1) and United states of Pharmacopoeia (USP) <1225> guidelines, and found to be accurate, specific, precise, linear, robust and stability-indicating. The precision and intermediate results were <5% CV for all the impurities. The accuracy for all the impurities was found to be between 90 and 110%. The linearity of regression co-efficient values for all the impurities were found to be more than 0.999.

CONCLUSION

The proposed related compounds method is found suitable for the determination of process and degradation impurities of commercial formulations, stability samples in QC analysis for PDT API, and drug product.

HIGHLIGHTS

The developed liquid chromatographic method greenness and eco-friendliness were assessed using the green analytical procedure index (GAPI) and the analytical greenness (AGREE) tool, and found to be green. A PDT detoxification procedure was also developed to reduce environmental pollution.

摘要

背景

本研究旨在采用绿色化学原理保护环境，开发了一种环保分析技术。培美曲塞是一种叶酸类似物，用于治疗晚期肺癌。

目的

开发一种用于定量测定原料药和注射剂中培美曲塞二聚体（PDT）有关物质的绿色稳定指示 HPLC 方法。

方法

采用 Zorbax SB C18 柱（150mm×4.6mm i.d.，3.5µ 粒径），以高氯酸盐缓冲液（pH3.0±0.1，50mM）为流动相 A，乙腈-高氯酸盐（90+10，v/v）缓冲液为流动相 B，流速 0.8mL/min，柱温 40°C±0.5°C，梯度洗脱分离所有分析物，总运行时间 75min。检测波长 230nm。

结果

该反相高效液相色谱法能够很好地分离 PDT 原料药和注射剂的所有降解产物和工艺杂质。有关物质方法符合国际协调会议（ICH）Q2（R1）和美国药典（USP）<1225>的验证要求，具有准确性、专属性、精密度、线性、耐用性和稳定性指示性。所有杂质的精密度均<5%CV。所有杂质的准确度均在 90%~110%之间。所有杂质的回归系数值的线性均大于 0.999。