Developments in Raman spectrometry and intracavity laser absorption spectrometry for quantitative analysis

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2010
Thesis identifier
  • T12744
Qualification Level
Qualification Name
Department, School or Faculty
  • A primary focus of this work was the investigation of reflectance mode and transmission Raman spectrometry for direct non-invasive quantitative analysis of a pharmaceutical tablet with < 3% w/w active ingredient (API). In the initial part of the study, an HPLC method was devised to quantify chlorpheniramine maleate (the API) in a sample set of more than 280 Chlortrimeton allergy tablets containing a stated API mass of 4 mg. Despite utilising a multi-stage, destructive sample preparation sequence, the average calculated API mass was found to be in good agreement with the stated mass. Nevertheless, sample anomalies were identified which suggested inconsistencies in the manufacturing process.Reflectance and transmission mode Raman spectrometry (herein referred to as solely reflectance and transmission Raman spectrometry) at a laser wavelength of 785 nm were then used to non-destructively analyse 380 Chlortrimeton tablets. With external calibration tablets, predictions of the API mass based on reflectance Raman spectra were in good agreement with the stated mass. However, predictions from transmission Raman spectra were less successful, with acceptable accuracy only achieved when there was a good match in the photon transmission properties of the calibration and sample tablets. An investigation of the effect of powder properties on the propagation of photons through diffusely scattering media was carried out; the magnitude of the transmission Raman signal obtained for any position of a Raman active layer of flowers of sulphur within or on the surface of the loose powder was found to be dependent upon the size and shape of the particles of the powder. The findings helped explain the results of the tablet analysis.In addition to investigating Raman spectroscopy as an alternative technique to HPLC for the determination of the API mass in tablets, the feasibility of developing an intracavity laser absorption spectrometry (ICLAS) system for liquid analysis, with the intention of using it as alternative detector to those commonly used in HPLC, was also investigated. It was demonstrated that ICLAS is capable of enhancing the absorption of analytes in liquid samples by utilising a multipass effect of radiation through the sample. ICLAS measurements acquired using a cavity operating at 860 nm constructed on an optical bench, and operated at an input current of 1.25 times the threshold current, provided an enhancement factor of x14. The magnitude of the enhancement observed depended on the input current utilised and how suited this was to the concentration range being analysed. A compact ICLAS system was constructed, but could not replicate the analysis carried using the optical bench set-up – highlighting the difficulties associated with ICLAS analysis of liquids.
Advisor / supervisor
  • Littlejohn, David
  • Nordon, Alison
Resource Type
Date Created
  • 2010
Former identifier
  • 820796