基于多元分析和响应面建模的反相高效液相色谱-光电二极管阵列法分析伏格列波糖和瑞格列净恩格列净。

Multivariate Analysis and Response Surface Modeling to Green Analytical Chemistry-Based RP-HPLC-PDA Method for Chromatographic Analysis of Vildagliptin and Remogliflozin Etabonate.

机构信息

Maliba Pharmacy College, Department of Quality Assurance, Maliba Campus, Bardoli-Mahuva Road, Tarsadi, Mahuva, Surat, Gujarat 394 350, India.

Swami Ramanand Teerth Marathwada University, School of Chemical Sciences, Nanded, Maharashtra 431 606, India.

出版信息

J AOAC Int. 2023 May 3;106(3):601-612. doi: 10.1093/jaoacint/qsad013.

DOI:10.1093/jaoacint/qsad013

PMID:36651669

Abstract

BACKGROUND

The fixed-dose combination (FDC) of vildagliptin (VDG) and remogliflozin etabonate (RGE) is used as antidiabetic medicine. Numerous reverse phase high-pressure liquid chromatographic (RP-HPLC) methods have been reported for the estimation of VDG and RGE using toxic organic solvents such as acetonitrile and methanol. These organic solvents are also hazardous to the environment.

OBJECTIVE

Hence, the robust and green analytical chemistry-based RP-HPLC-PDA method has been developed for chromatographic analysis of VDG and RGE for the safety of analysts and protection of the environment.

METHOD

The multivariate analysis has been carried out for the identification of critical method risk parameters (CMRPs) and critical method performance attributes (CMPAs) using principal component analysis (PCA). The identified CMRPs and CMPAs were linked with each other for optimization of the RP-HPLC-PDA method using DoE-based response surface modeling. The analytical design space (ADS) has been explored for robust chromatographic analysis of VDG and RGE.

RESULTS

The chromatographic analysis of VDG and RGE has been carried out using Shim-Pack C18 column (250 mm L, 4.6 mm ID, 5.0 µm PS) and isopropyl alcohol-0.1% (v/v) formic acid (FA) in water (45 + 55, v/v, pH -3.5). The developed method has been validated in accordance with ICH Q2 (R1) guidelines. The method has been applied for the assay of VDG and RGE in their FDCs. The results of the assay were found in compliance with the labeled claims.

CONCLUSIONS

The developed RP-HPLC-PDA method did not include any toxic or carcinogenic solvents. Hence, it is safe for analysts and the environment. The greenness profiles of the published and proposed RP-HPLC methods were evaluated by the national environmental method index (NEMI) scale, and the analytical greenness scores were calculated using the AGREE software. The developed method can be used as an eco-friendly tool in the pharmaceutical industry for routine analysis and quality control of FDCs of VDG and RGE.

HIGHLIGHTS

Development of a green and robust RP-HPLC method for the estimation of VDG and RGE using safe organic solvents. The analytical quality by design (AQbD) approach has been implemented in the development of a method to minimize solvent wastage. The method was applied for the assay of FDCs of VDG and RGE.

摘要

背景

维格列汀（VDG）和瑞格列净乙酯（RGE）的固定剂量组合（FDC）被用作抗糖尿病药物。已经报道了许多使用有毒有机溶剂（如乙腈和甲醇）的反相高效液相色谱（RP-HPLC）方法来估算 VDG 和 RGE。这些有机溶剂对环境也有危害。

目的

因此，已经开发了基于稳健和绿色分析化学的 RP-HPLC-PDA 方法，用于 VDG 和 RGE 的色谱分析，以确保分析人员的安全和保护环境。

方法

使用主成分分析（PCA）对多变量分析进行了识别，以确定关键方法风险参数（CMRPs）和关键方法性能属性（CMPAs）。将鉴定出的 CMRPs 和 CMPAs 相互关联，以使用基于设计的响应面建模优化 RP-HPLC-PDA 方法。为 VDG 和 RGE 的稳健色谱分析探索了分析设计空间（ADS）。

结果

使用 Shim-Pack C18 柱（250mm L，4.6mm ID，5.0µm PS）和异丙醇-0.1%（v/v）甲酸（FA）在水中（45+55，v/v，pH-3.5）进行了 VDG 和 RGE 的色谱分析。该方法已按照 ICH Q2（R1）指南进行验证。该方法已用于测定其 FDC 中的 VDG 和 RGE。测定结果符合标签要求。

结论

所开发的 RP-HPLC-PDA 方法不包含任何有毒或致癌溶剂。因此，它对分析人员和环境是安全的。通过国家环境方法指数（NEMI）量表评估了已发表和建议的 RP-HPLC 方法的绿色度概况，并使用 AGREE 软件计算了分析绿色度评分。所开发的方法可作为制药行业的一种环保工具，用于常规分析和 VDG 和 RGE 的 FDC 的质量控制。