GC-MS methods for drugs

[G.Patton]

Introduction:

I have extensive experience in determining the quality of drugs by chromatography-mass spectrometry. I decided to write this instruction for chemists, who want to begin testing drugs by GC-MS equipment.
Despite the wide range of chromato-mass spectrometry opportunities there are limitations of the possibilities. Mass detector in tandem with chromatograph can't determine inorganic substances, organic substances with molecular weight more than 450 Da or organic substances with high boiling temperature (>350 ◦C).​

Equipment characteristics:

At first, you have to define your possibility to provide analysis using your gas chromatograph. Most popular appropriate GC-MS systems as Agilent 7890 gas chromatograph, coupled to an Agilent 5975C quadrupole mass detector or Thermo Scientific ISQ 7000 Single Quadrupole GC-MS could be used for these goals. The main characteristic, which you need to know – it is polarity of a capillar column. For the majority of drugs, you need non-polarity or weakly polar capillary column. For instance, HP-1/DB-1 or HP-5/DB-5 are the best choice for a wide range of applications. Also, you need to know the range of mass, which your mass-detector can detect in SCAN mode. Usually, you require 30-450 m/z range, it is enough to determine all type of drugs. Most of them could be established between 30-350 m/z.​

Sample preparation procedure:

All drugs stay in salt form due to higher stability, which allow keeping them long time without structural changings. For example, amphetamine has nitrogen atom, it is the base, which is bounded with acid ion(s) as 2-(SO4), -Cl, 3-(PO4). You need to obtain the free-base of analysis substance. Also, if you don’t know what a substance you’ve got for analysis, you have to carry on experiment for qualitative determination using reagents, which I mentioned earlier(Drugs testing reagents).

Universal preparing will be quite simple. Place the aliquot of the sample into a flask and fill it with a pure solvent (CCl4/ CH2Cl2). Prepare approximately 10-1000 mkg/ml of the solution. Most of narcotic substances could not be solved in carbon tetrachloride/dichloromethane. After, you need to add 1-2 volume of 30-40% NaOH/KOH aqueous solution in this flask with drug solution and mix it thoroughly.

Almost same preparation is used for marks(LSD, NBOMe, NBOH etc.). Take a mark with declared amount of substance and cut it into flask, add pure solvent (CH2Cl2 is recommended). Prepare approximately 10-1000 mkg/ml of the solution. After, you need to add 1-2 volume of 30-40% NaOH/KOH aqueous solution in this flask with drug solution and mix it thoroughly.

You will obtain free-base of analysed drug, which will migrate to the organic solvent layer. You have to inject 1 mkl drug solution and start analysis.​

GC-MS methods.
For the vast range of drugs:

The GC–MS system operating at 70 eV in electron ionisation mode. The apparatus is equipped with a 5% phenyl-methylsilicone capillary column (30 m × 0.25 mm i.d., 0.25 m film thickness). Helium is used as carrier gas at a constant flow of 1 mL/min. The chromatographic conditions were set as follows: The oven temperature hold at 130 ◦C for 2 min, increase to 270 ◦C at 15 ◦C/min. The injection port set at 270 ◦C in split mode with split raito 25:1. The mass detector operates in scan mode (scan range from m/z 30–390).​

For LSD, NBOMe, NBOH marks:

The GC–MS system operating at 70 eV in electron ionisation mode. The apparatus is equipped with a 5% phenyl-methylsilicone capillary column (30 m × 0.25 mm i.d., 0.25 m film thickness). Helium use as carrier gas at a constant flow of 1 mL/min. The chromatographic conditions set as follows: The oven temperature hold at 40 ◦C for 2 min, increase to 210 ◦C at 15 ◦C/min, after increase to 280 ◦C at 5 ◦C/min and hold 20 min. The injection port set at 280 ◦C in splitless mode. The mass detector was operated in scan mode (scan range from m/z 30–450).​

Conclusion:
As you can see, preparation of samples is quite simple. It doesn't need expensive reagents or difficult manipulations. However, this procedure very important to obtain relevant analysis results.

 

[Cocojamba]

What about another GC-MS systems? Or these methods work only with Agilent or Thermo Scientific?

 

[G.Patton]

In fact, no, you can use any system with the same specifications.