Mr. Aziz,

Regarding your question, you could focus your attention on paper [1], dealing with the same topic in particular talking about sample preparation.

[1] Methods Mol Biol, 1198 (2014) 251-63; doi: 10.1007/978-1-4939-1258-2_16.

Analysis of volatile organic compounds in exhaled breath by gas chromatography-mass spectrometry combined with chemometric analysis

J. Dallinga, A. Smolinska, F. van Schooten

Towards, your quantification methods, however, there are serious constrains, looking at the MS method performances according to the currently available quantitative protocols. In other words, the current quantitative protocols operate at lower reliability of the data, comparing with the real capability of the mass spectrometric method, which provides, in fact, absolute quantification of the analytes, however, using not the known standard quantitative approaches for data-processing.

Owing to the fact that for the clinical diagnostics it is of paramount importance an obtaining of the most accurate, precise, selective and sensitive analysis at the lowest possible LODs, I recommend you to focus attention on our most recently developed and our own authored stochastic dynamic approach and model formulas for quantitative treatment of the experimental mass spectrometric variables ''intensity'' [2]. The method yields to absolute quantification of the analytes (coefficients of correlations up to /r/ = 1) at pg.(mL)-1 and ng.(L)-1 concentrations of analytes in mixture.

[2] Steroids, 164 (2020) 108750

Stochastic dynamic mass spectrometric quantification of steroids in mixture — Part II; Bojidarka Ivanova, Michael Spiteller

If you have any questions concerning the direct application of the our approach to routine analysis in the clinical practice, do not hesitate to ask us, herein. We shall provide to you the most comprehensive guidelines for our innovative quantitative concept for treatment of mass spectrometric data step-by-step. Some, calculation tasks have been detailed [3].

[3] Bioorganic Chemistry; 93 (2019) 103308

A mass spectrometric stochastic dynamic diffusion approach to selective quantitative and 3D structural analyses of native cyclodextrins by electrospray ionization and atmospheric pressure chemical ionization methods

Bojidarka Ivanova; Michael Spiteller

You'll need a gas phase sampler attached to the GC. The typical liquid injector doesn't work for your application.

Check out this website to have an idea about gas phase autosampler for analyses of captured gases: https://www.entechinst.com/store/lab-instrumentation-gc-accessories/7650-L-20-gc-gas-autosampler/

The canisters are used to carry the gas phase sample, they should serve the purpose of the typical glass vials that carry the liquid phase sample.

Last thing to note is the sample collection from subjects of your study. I am not aware of the medical field so I can't say for sure this gonna work, but I've seen in a medical pathology lab they use a bag to collect sample of human breath by asking the subject to blow through one point in the bag and whatever collected in the bag won't leave it because of the design. So maybe this is a way you can collect breath samples in a gas phase and use the gas phase autosampler to inject them into the GC.

For abundant VOCs you can simply collect samples to TEDLAR bags and inject 0,2-0,5mL by gastight syringe to your GC.

However, the best option would be to trap the VOCs dirextly from patients using sorption tubes (for example with TENAX sorbent). For this case you need however a thermal desorber attached to your GC.

Single quad MS is ok for this purpose you don't need more. Chack my papers on VOCs analysis.

Regards

GB

Dear Shahid Aziz thank you for your interesting question. For some additional information please also see the following potentially useful references:

1. A rapid method for the analysis of air toxics based on US EPA TO-1

2. Routine analysis of volatile organic compounds in drinking water with ISQ 7000 GC-MS

(see attached pdf files)

If you are obligated to use a liquid sampler and inlet configuration you may use a breathalyzer coupled with appropriate VOC-trapping adsorbents for sampling. Carbon disulfide and methanol single pot combined or sequential elution from adsorbent can be used for target VOC identification.