Objectives: Nicotine lactate, nicotine tartrate, nicotine benzoate and freebase nicotine (FBN) are four forms of nicotine delivery systems presented or used in tobacco products, for example, e-liquids for electronic cigarettes. So, compare their pharmacological (pK) efficacies are important to understand their roles in addiction and abuse liability of the tobacco products.

Methods: In this work, the pK of the above nicotine systems were studied by injecting their aqueous solutions subcutaneously in rats, and the blood samples were collected from the jugular vein. The levels of nicotine in the blood were analyzed by LC-MS/MS.

Results: The results showed that rapid nicotine absorption occurred for all the nicotine systems, among them, NB has the smallest Tmax, while FBN has the largest Tmax. The nicotine metabolic rate and clearance decreased for FBN, indicating that the maintain of nicotine in the body was higher than that of the other three salt-based systems. In addition, with increased benzoic acid ratios, the Cmax of the nicotine benzoate (NB) in the plasma was decreased, indicating that the lower the pH, the lower the Cmax. When different concentrations of NB were used, the higher the NB concentration, the greater the Cmax and AUC.

Conclusion: Compared with the nicotine salts, FBN could reach and maintain a higher concentration in animal model. And the nicotine adsorption by NB in the animal model was both pH and concentration dependent. The baseline information could be used to explain different clinical pharmacological observations in human.