Series 3 - Analytical Method

-

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 caution to find the most optimum LC/GC column to enhance the amines retention, and further derivatisation may also be required.
2) Most amines are volatile compounds with a low boiling point
  • In this case, GC and IC may be more appropriate for volatile compounds than HPLC/UPLC.
3) Amines have relatively small molecular weights
  • MS detector is considerable due to its exceptional sensitivity for identifying compounds by their specific mass.

 

Figure 1. Ion Chromatography Instrumentation
(Source: https://serc.carleton.edu/microbelife/research_methods/biogeochemical/ic.html)


Then, what ...?


References:
  1. B. Tuesuwan and V. Vongsutilers, J Pharm Sci, 2021, 110, 3118–3128.
  2. G. C. Graffius, B. M. Jocher, D. Zewge, H. M. Halsey, G. Lee, F. Bernardoni, X. Bu, R. Hartman, E. L. Regardo, J Chrom A, 2017, 1518, 70-77.
  3. Z. Lewis, B. A. Jackson, A. Crampton, A. D. Ray, S. W. Holman, Rapid Commun Mass Spectrom, 2020, 34, DOI: 10.1002/rcm.8680.

Comments

Post a Comment

Popular posts from this blog

Series 5 - Research Insights

-
Image
5#  The findings After a month of research, I successfully obtained the ideal method set-up for separating eight amines and the Active Pharmaceutical Ingredient (Ibuprofen) compound. All mass spectrum I obtained has more than a 50% probability of similarity with the standard, according to the National Institute of Standards and Technology (NIST) Library software. Figure 1.  Peak Chromatogram of Dibutylamine (generated with Thermo Xcalibur™ 2.2 SP1.48) Figure 2.  Mass Spectrum of Dibutylamine (generated with Thermo Xcalibur™ 2.2 SP1.48) Figure 3.  NIST Mass Spectrum Search 2.0 Library Similarity Result for Dibutylamine Even though I still have a long way to run, the progress I have achieved so far may allow me to deliver some insights and findings: 1) D ifference in boiling point is the key to enhancing the separation. After identifying each analyte's boiling point, we will be able to optimise the oven temperature appropriately. Figure 4.  Oven Temperature Set-up in Thermo Xcali
Read more

Series 1 - Nitrosamine Introduction

-
Image
  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
Read more

Series 4 - Research Process

-
Image
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
Read more