RESEARCH REVERIES

4#  Initiate the research This section will ‘summarise’ what I am and will be doing in my research project based on the explanations I have delivered earlier. I am eager to explore the analysis of amines, specifically secondary amines , in the pharmaceutical sample matrix, which, surprisingly, has not had many similar published studies so far. There are many amine varieties in nature, and considering the safety aspect, here are my several choices of amines ( again, I will focus more on the secondary ones ): Diethanolamine, Dipropylamine, Diethylamine, Dibutylamine, Diisopropylamine, Pyrrolidine, Piperidine, and  N-methyl pyrrolidinone ( NMP) . While NMP is a tertiary amine, its presence should also be a warning due to its ability to generate secondary amine under certain conditions. I created a model solution for the sample matrix comprising Active Pharmaceutical Ingredients (APIs) and excipients to mimic the characteristics of an actual tablet drug but directly in solution form. M

3#  What is the analytical method for amines? In the previous section, it was clear why we must detect and quantify amines in drugs. This is possible by applying chromatography techniques, which may be preferable to spectrometry regarding specificity and selectivity. Several chromatography instruments are available for amines, including High-Performance Liquid Chromatography/Ultra-Performance Liquid Chromatography (HPLC/UPLC), Gas Chromatography (GC), and Ion Chromatography (IC), with a variety of detectors, such as Mass Spectrometry (MS), Flame Ionisation Detector (FID), and Conductivity Detector (CD). But how can we determine which instrument to use? First, we must investigate amines' chemical characteristics more thoroughly. 1)  Amines are polar compounds due to the presence of electron lone pairs in the nitrogen; this may indicate: IC may be appropriate, as it is promising to provide excellent separation. Reversed-phase HPLC/UPLC and GC are also still applicable, but with cau

2#  What causes nitrosamines presence?   Technically, nitrosamines may be present due to contamination or intrinsic formation by the reaction of two existing essential components during the manufacturing process: 1) amines and 2) nitrites, under certain conditions (heat, pH, and water content). All amines, including primary, secondary, tertiary, and quaternary, can possibly form nitrosamines. However, secondary amines are the most reactive ones, as they can react directly with nitrites and produce stable nitrosamines (see Figure 1).   Figure 1. The Primary, Secondary, and Tertiary Amine Reaction with Nitrites Drug products comprise Active Pharmaceutical Ingredients (API) and additive substances called excipients. Amines may exist in the drug product, such as in the API structure formula or from excipients, as well as solvents or reagents used in manufacturing. Several common solvents used are Dimethylformamide (containing Dimethylamine as secondary amines) and N-methyl pyrrol

  1#  What are nitrosamines? First found 100 years ago, nitrosamines never received the spotlight in the pharmaceutical or chemistry world, as happened earlier in 2018. Back then, the world was shocked by the United States Food and Drug Administration's (US-FDA) discovery of one of the nitrosamine compounds, N-Nitrosodimethylamine (NDMA) , contaminating the Valsartan drug beyond acceptable levels. Valsartan is one of the hypertension drugs that works by relaxing blood vessels to prevent heart failure and its complications. This discovery led to a massive voluntary recall of Valsartan drug across all drug manufacturer companies worldwide, which later caused a drug shortage phenomenon. Figure 1. Valsartan Tablets ( Source:  https://www.aboutlawsuits.com/valsartan/ ) Maybe we all wonder why these actions are necessary. This NDMA compound was identified as a carcinogenic compound that may cause cancer, and its presence in vast amounts in life-saving drugs is undoubtedly a serious