Investigation of various analytical methods for the identification and quantification of active pharmaceutical ingredients
The pharmaceutical industry depends heavily on analytical techniques for controlling and improving the quality of products. Development generally focuses on the sensitivity, selectivity, and efficiency of the technique and portability of the analytical instrument. Inductively coupled plasma mass spectrometry (ICP-MS) is a wellestablished method for metal determinations. However, fewer investigations have focused on ICP-MS for nonmetal detection. One of the reasons is the high ionization energies of nonmetals. In this dissertation, the use of an ICP-quadrupole MS combined with ultrasonic nebulization-membrane desolvation for sample introduction to determine and quantify phosphorus, sulfur, chlorine and fluorine heteroatom-containing active pharmaceutical ingredients is presented. Detection limits obtained were comparable to those obtained by high-resolution instruments because the use of ultrasonic nebulization and membrane desolvation provided high analyte transport efficiency and highly efficient solvent removal ability, respectively. Raman spectroscopy is a popular tool for qualitative determinations of molecular structures and properties. However, only in recent years is it being used for quantitative analysis with the advancements of chemometrics. In this dissertation, the use of dispersive Raman spectroscopy combined with multivariate calibration and various data preprocessing methods to quantify acetaminophen, guaifenesin, and phenylephrine hydrochloride is presented. The application of this method to the quantification of these three active pharmaceutical ingredients in an over-the-counter drug was successful, with absolute differences in the range of 0.3 to 3.3 % compared to the labeled values. Although Raman spectroscopy is an excellent technique for chemical analysis, Raman instruments are traditionally stationary and bulky in size. More portable and lighter instruments are often required in an industrial setting. Acousto-optic tunable filters (AOTF) are compact solid-state devices that can be used as wavelength selectors. In this dissertation, the feasibility of the application of an ultra-violet AOTF for Raman spectroscopy is presented. High background signal from Rayleigh and laser scattering was determined to be the limiting factor causing the Raman signal to be undetectable using this ultra-violet AOTF.