Improving the efficiency of ion mobility spectrometry analyses by using multivariate calibration

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Ion mobility spectrometry (IMS) offers speed and sensitivity for active pharmaceutical ingredient (API) determination.
• Poor resolution in IMS hinders analysis of compounds with similar molecular weights, like those in oral contraceptives.
• Ethinylestradiol (ETE) and desogestrel (DES) are low-concentration APIs in oral contraceptives with overlapping peaks in IMS.

Purpose of the Study:

• To assess the potential of IMS for detecting and quantifying ETE and DES in commercial oral contraceptive tablets.
• To improve IMS resolution for analyzing low-concentration APIs with similar properties.

Main Methods:

• Utilized chemometric techniques, including a second-derivative (TN2D) algorithm and Multivariate Curve Resolution (MCR), to enhance peak separation.
• Developed quantitative models using Partial Least Squares regression (PLS1) for individual API determination.
• Validated the method for routine analysis, focusing on speed and sample volume.

Main Results:

• Successfully resolved overlapped peaks of ETE and DES using MCR and TN2D.
• Achieved high accuracy in quantitation with PLS1 models, showing >98.4% Y-explained variance.
• Obtained low Root Mean Square Error of Prediction (RMSEP) values: 0.34 for ETE and 0.63 for DES.
• Demonstrated an expeditious method with analysis times under 1 minute and minimal sample requirements.

Conclusions:

• IMS, enhanced by chemometrics, shows significant potential for accurate qualitative and quantitative determination of low-dose APIs in pharmaceuticals.
• The developed method is suitable for routine analysis due to its speed, sensitivity, and minimal sample requirements.