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New sampling techniques in gas chromatography applied to a pharmaceutical context


The determination of small amounts of RS in solid samples that are difficult to dissolve like MPSi, gelatine and albumin is not evident. Conventional HS-GC has difficulties to deliver reliable results for this type of samples. In this study, the application of TD-GC in a modified mode has been investigated. So, samples were sandwiched between 2 double layers of QF in a TD tube.

In chapter 2, an easy-to-apply TD-GC method has been developed and validated for the determination of 7 RS commonly used for drug loading of MPSi. MPSi displays some specific properties in terms of adsorption and active surface area. The method showed excellent sensitivity, linearity, recovery and repeatability and was finally applied on drug loaded MPSi. An independent HS-GC method following HF treatment to destroy the matrix has also been applied to compare with. There was no significant difference in the results obtained from the two methods. However, the HS-GC method needs complicated sample preparation steps and is less suitable from a practical point of view.

In chapter 3, the application of TD-GC for quantitative determination of residual DMSO in solid gelatin has been investigated. The proposed method was successfully optimized and validated. Another approach based on the complete enzymatic digestion of gelatin combined with dehydratation followed by HS-GC was developed and applied to verify the proposed method. Quantitative results were in good agreement.  Unlike HS-GC, TD-GC does not require to select a suitable solvent to dissolve the sample. As a result, there is no interference in the chromatogram from a large solvent peak nor from impurities present in the solvent. In addition, since the sample size in TD can be eventually further increased, it is possible to improve the sensitivity.

In chapter 4, the ILC system – based on a modified GC injector installed on the TD instrument has been proposed. This allowed to evaluate properly the OLC approach by injecting standard solutions on sample tubes containing each 4 QF disks, a single size MPSi bed or a mixed MPSi bed immobilized in a TD tube. For the MPSi beds, loading was performed with and without sweep gas during injection by connecting the tube to an injector port with a flow of N2. Based on the obtained results, it was possible to confirm that there was incomplete transfer of reference substances during OLC due to tube operation, especially when only QF was used. This improved when MPSi was added as sorbent and the presence of a sweep gas minimized the differences with ILC. For the investigated volatile organic compounds, apart from DMSO, ILC surpasses OLC in terms of transfer ratio.

Finally, in chapter 5, work around the use of TD-GC for the determination of RS in albumin has been presented. Calibration was performed with OLC (tube with a mixed MPSi bed loaded under a sweep gas flow) as well as ILC to check if the transfer of the calibrants with OLC was complete. An independent method based on the complete enzymatic digestion of albumin combined with HS-GC was applied to verify the complete release of analytes from the albumin. Both the proposed TD-GC and HS-GC methods were applied for the determination of residual EtOH and DCM in two drug loaded albumin samples. The results obtained by the two methods were comparable. However, the TD-GC method is easier and more practical, illustrating once more its great and interesting potential.

Date:1 Oct 2014  →  18 Sep 2018
Keywords:TD-GC/MS, Residual solvents, Mesoporous silica, gelatin
Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences, Analytical chemistry, Pharmaceutical analysis and quality assurance, Chemical product design and formulation, Biomaterials engineering
Project type:PhD project