Samenvatting

Over the period February 2023 to July 2023, the aim was to develop a method for the determination of endotoxin in pharmaceutical products according to GMP rules. To bring this research to a successful conclusion, the intention was to demonstrate endotoxins in pharmaceutical products using the Kinetic Turbidimetric Limulus Amebocyte Lysate method and the Kinetic Quantitative
Chromogenic Limulus Amebocyte Lysate method. The measurements would take place using an Ultraviolet-Visible Light spectrophotometer Cary 100. The intention was to ensure the developed method also would be cost efficient. After 18 weeks of research, the following conclusions can be drawn: The theoretical research into the Ultraviolet-Visible Light spectrophotometer has shown that setting up an endotoxin method with the Ultraviolet-Visible Light spectrophotometer seems not to be a cost effective method. Too many reagents would be used per measurement, resulting reagent costs that are too high. After 7 weeks, it was decided to investigate several devices for a preferred method for endotoxin determination. For Brightlabs , this investigation provided the insight the BioTek Elx08 with Agilent Gen5 Software is the most cost-efficient device to perform an endotoxin determination. As a next step, Brightlabs decided to continue working with the Kinetic Quantitative Chromogenic Limulus
Amebocyte Lysate method only. This method is the most sensitive endotoxin determination method, and it is cost efficient to perform only one of the two methods. In addition, this study investigated which supplier of the reagents/products would be the most advantageous. It turned out FUJIFILM Wako had the most advantageous price, in terms of reagents per analysis.
Based on these experiences, an analytical method was developed, in which the GMP rules have been incorporated. The GMP rules originated from the EUROPEAN PHARMACOPOEIA 11.0 2.6.14 and USP <85>. Due to the time limit, the research “drawing up a method for the endotoxin determination in pharmaceutical products adhering to GMP rules” only has been worked out theoretically.
In this study, the practical results are based on the Ultraviolet Visible-light measurements. In the first 7 weeks, two tests were carried out to master the technique of the Ultraviolet-Visible Light spectrophotometer. In these two tests, the active substance acetaminophen in paracetamol was measured. These two measurements resulted in clarity on the technique how to utilize the
Ultraviolet-Visible Light spectrophotometer. In addition, the conclusion was 1 tablet of paracetamol contains 78.69% mg/tablet acetaminophen (the active substance of paracetamol).