Publication Date

Fall 2016

Document Type

Thesis

Degree Name

Master of Science

Department

Analytical Chemistry

First Advisor

Shailendra Kumar, Ph.D.

Second Advisor

Joong-Won Shin, Ph.D.

Third Advisor

Walter Henne, Jr., Ph.D.

Abstract

Quantitative analysis is an important step during pharmaceutical drug development. Currently, the pharmaceutical industry uses high performance liquid chromatography (HPLC) for quantitative analysis of organic compounds as the preferred technique. The proton nuclear magnetic resonance (NMR) technique has an inherent ability to quantify a given analyte and may be used to quantify organic compounds. Quantitative nuclear magnetic resonance spectroscopy (q-NMR) of acetylsalicylic acid (ASA) was conducted using tert-butyl alcohol (tert-butanol) as the internal standard and deuterated chloroform (CDCl3) as the solvent. Preparations of ASA solutions in low and high concentration ranges, 1.0 mM – 10.1 mM and 10.0 mM – 100.1 mM respectively, were analyzed to determine a linear correlation between the concentrations of ASA with the intensities of methyl peaks and aromatic ring proton peaks using Topspin software.

The q-NMR analysis of high concentration ASA solutions showed a strong linear correlation (R2 values > 0.9994) and high precision (% RSD values < 1%) for both the average methyl peak areas and the average aromatic ring proton peak areas. However, the low concentration ASA solutions showed a weak linear correlation (R2 values > 0.9914) but, fairly good precision (% RSD values < 5%) for both the average methyl peak areas and the average aromatic ring proton peak areas. Therefore, the q-NMR technique is a viable alternative for quantitative analysis of high concentration ASA methyl peak areas and aromatic ring proton peak areas, but it is not suitable for the low concentration ASA solutions.

The low concentration (1.0 mM – 10.1 mM) ASA solutions were also analyzed by the conventional HPLC method; the results obtained were compared with the results from the q-NMR technique. A comparison of q-NMR data to HPLC data focused on linearity, precision, and acquisition time for the acetylsalicylic acid solutions at low concentrations. The HPLC data showed a strong linear correlation with an R2 value of 0.9997 and high precision with a % RSD < 0.9% for the average ASA peak areas. A comparison of q-NMR data to HPLC data for the low concentration ASA solutions showed that the q-NMR technique used less solvents and less time for data acquisition.

Download

Share

COinS