Isotopically-labeled solvents and the use of same in testing E-cigarettes
Isotopically-labeled species of propylene glycol and glycerol are provided as solvents for use in electronic nicotine delivery systems (e.g., as disposed in a cartridge in an e-cigarette). The isotopically-labeled species are distinguishable from the non-isotopically-labeled species (e.g., by mass spectrometry). Thus, methods are provided for the measurement of the quantity of solvent or of a solvent heating by-product (e.g., formaldehyde, acetaldehyde), or of a metabolite of the drug, delivered to a user by analysis of blood samples taken subsequent to dosing by use of the electronic nicotine delivery system. An example of an isotopically-labeled species of propylene glycol for use in such measurement methods is [ 13 C] 3 H 8 O 2 . A clinical study of e-cigarettes loaded with this isotopically-labeled species resulted in the following blood plasma concentration profiles in “vaping” subjects.
1. A method of determining a quantity of a compound delivered to a user of an e-cigarette comprising:
providing a user with an e-cigarette including an e-cigarette cartridge loaded with a liquid that includes a predetermined quantity of solvent that includes non-radioactive isotopically labeled propylene glycol that is isotopically enriched by at least three atomic mass units;
dosing the user with said e-cigarette;
obtaining a bodily fluid sample from the user; and
determining the amount of isotopically-labeled propylene glycol in the bodily fluid by measuring the concentration of isotopically-labeled propylene glycol in the bodily fluid sample.
2. The method according to claim 1 , wherein said liquid further comprises nicotine.
3. The method according to claim 2 , wherein the concentration of said nicotine in said liquid is between about 0.3 and about 4.0 v/v %.
4. The method of claim 1 , wherein the bodily fluid sample is a blood sample.
5. The method of claim 4 , wherein the level of isotopically-labeled propylene glycol in a blood plasma portion of the blood sample is measured using mass spectrometry.
6. The method of claim 1 , wherein the bodily fluid sample is a saliva sample.
7. The method of claim 6 , wherein the level of isotopically-labeled propylene glycol in the saliva sample is measured using mass spectrometry.
8. The method of claim 1 , wherein the bodily fluid sample is a urine sample.
9. The method of claim 8 , wherein the level of isotopically-labeled propylene glycol in the urine sample is measured using mass spectrometry.
10. The method of claim 1 , wherein only the carbon atoms of the propylene glycol are isotopically weighted.
11. The method of claim 1 , wherein only the hydrogen atoms of the propylene glycol are isotopically weighted.
12. The method of claim 1 , wherein only the hydrogen atoms and oxygen atoms of the propylene glycol are isotopically weighted.
13. The method of claim 1 , wherein the carbon atoms, hydrogen atoms and carbon atoms of the propylene glycol are each isotopically weighted.
14. The method of claim 1 , wherein only the carbon atoms and oxygen atoms of the propylene glycol are isotopically weighted.
15. The method of claim 1 , wherein only the hydrogen atoms and carbon atoms of the propylene glycol are isotopically weighted.
16. An e-cigarette loaded with a mixture including propylene glycol that is isotopically enriched by at least three atomic mass units.
17. The e-cigarette of claim 16 , wherein the mixture further includes nicotine.
18. The e-cigarette of claim 17 , wherein the concentration of said nicotine in said mixture is between about 0.3 and about 4.0 v/v %.
19. A cartridge for an e-cigarette wherein the cartridge is loaded with a mixture including propylene glycol that is isotopically enriched by at least three atomic mass units.