The Stages behind Developing a New Drug in Industry … Part 2

Following the diagram presented in Part 1, the Drug Discovery stage begins with the identification of a target site that is linked to a disease. (Note: some researchers refer to this as the pre-Drug Discovery stage.)

The main goal behind the Drug Discovery stage is to identify or envision a hit compound(s) that can offer some potential for activity at the target site. A hit compound(s) is uncovered from an array of resources such as: natural products, de novo, high-throughput screening, biotechnology, serendipity, searching across structural libraries, past experiences on similar targets, etc. The hit compound(s) is validated, and barring any toxicity issues, the compound is transitioned from hit to lead compound for the next stage of the development process Drug Design.

The Innovation website presents a similar description on drug development in industry. It also includes a nice movie summarizing the development.

The Stages behind Developing a New Drug in Industry … Part 2

Following the diagram presented in Part 1, the Drug Discovery stage begins with the identification of a target site that is linked to a disease. (Note: some researchers refer to this as the pre-Drug Discovery stage.)

The main goal behind the Drug Discovery stage is to identify or envision a hit compound(s) that can offer some potential for activity at the target site. A hit compound(s) is uncovered from an array of resources such as: natural products, de novo, high-throughput screening, biotechnology, serendipity, searching across structural libraries, past experiences on similar targets, etc. The hit compound(s) is validated, and barring any toxicity issues, the compound is transitioned from hit to lead compound for the next stage of the development process Drug Design.

The Innovation website presents a similar description on drug development in industry. It also includes a nice movie summarizing the development.

The Stages behind Developing a New Drug in Industry

Many new medicinal drugs produced by pharmaceutical companies follow a very similar pathway starting from the inception of the project idea and ending at the shelves of a pharmacy. Each stage in the development of the drug involves various types of chemists, each lending their expertise at synthesizing, extracting, analyzing and testing the new drug.

The following diagram presents a simplified summary in the development of a medicinal drug. The general stages are 1. Drug Discovery, 2. Drug Design, 3. Drug Trials and 4. Drug Manufacturing/Process.

 

 Please note that this overview may not apply to all cases.

The Stages behind Developing a New Drug in Industry

Many new medicinal drugs produced by pharmaceutical companies follow a very similar pathway starting from the inception of the project idea and ending at the shelves of a pharmacy. Each stage in the development of the drug involves various types of chemists, each lending their expertise at synthesizing, extracting, analyzing and testing the new drug.

The following diagram presents a simplified summary in the development of a medicinal drug. The general stages are 1. Drug Discovery, 2. Drug Design, 3. Drug Trials and 4. Drug Manufacturing/Process.

 

 Please note that this overview may not apply to all cases.

My Column is Bleeding

Whenever a GC column is used to identify and/or quantify a sample, the column stationary phase can bleed into the MS source along with the sample. High column bleed can hinder the analysis of a sample. The resulting spectral interference typically manifests itself as discrete peaks and/or an increase in the drift of the baseline, which in turn, produces data with low signal-to-noise and poor sensitivity.  

The GC-EI mass spectra below are two examples showing high column bleed. The ion peaks at m/z 73, 133, 193, 207, 267, 281, 355 and 429 are not part of the purified sample but pertain to the column stationary phase. The major column bleed ion, m/z 207, is a result of the formation of hexamethylcyclotrisiloxane. The presence of these characteristic masses for siloxanes indicates there is a significant column bleed and that the column may need replacing.

  

My Column is Bleeding

Whenever a GC column is used to identify and/or quantify a sample, the column stationary phase can bleed into the MS source along with the sample. High column bleed can hinder the analysis of a sample. The resulting spectral interference typically manifests itself as discrete peaks and/or an increase in the drift of the baseline, which in turn, produces data with low signal-to-noise and poor sensitivity.  

The GC-EI mass spectra below are two examples showing high column bleed. The ion peaks at m/z 73, 133, 193, 207, 267, 281, 355 and 429 are not part of the purified sample but pertain to the column stationary phase. The major column bleed ion, m/z 207, is a result of the formation of hexamethylcyclotrisiloxane. The presence of these characteristic masses for siloxanes indicates there is a significant column bleed and that the column may need replacing.

  

Ah Sugar, Sugar … Residue

Sugar residues (saccharides) can be tough to elucidate. They tend to have 1H NMR spectrum with overlapping and sometimes poorly-resolved 1H signals, and the 2D NMR data presents lots of ambiguous assignments. With a little practice, an elucidator can quickly pick out a sugar moiety based on a minimal amount of NMR data.

For a given set of atoms with known 13C chemical shifts (shown below), a hexopyranoside sugar moiety is evident even without any long-range coupling information. The general pattern is as follows: a CH at ~100 ppm, 4 CHs between ~70 to 77 ppm, a CH2 at ~60 ppm, 6 O atoms and 4 H atoms. Note: the H atoms count may vary depending on the number of connection points.

An example sugar, phenyl hexapyranoside, with 13C chemical shifts is presented below.