Characterization of pharmacokinetics of 2-(3-(chloromethyl)benzoyloxy)benzoic acid in rats

  • Caroline Widya Mandala Catholic University
  • Nathania Sie Widya Mandala Catholic University
  • Kuncoro Foe Widya Mandala Catholic University
  • Senny Yesery Esar Widya Mandala Catholic University
  • Maria Anabella Jessica Widya Mandala Catholic University


A new compound of salicylic acid derivative, namely 2-(3-(chloromethyl)benzoyloxy)benzoic acid (3CM), was synthesized in order to find a compound exhibiting higher analgesic activity and smaller ulcer irritation than acetylsalicylic acid (ASA). In this study, the pharmacokinetics of this new compound in rats was investigated, following a single dose oral administration of 3CM (45 mg/kg BW). Plasma samples of 9 healthy rats were collected before and up to 3-hours after its oral administration, following an 18-hour fasting period. Plasma concentrations of 3CM were determined using a validated HPLC-DAD assay. Pharmacokinetic parameters were determined using compartment model technique. All experiments were carried out in triplicate. The pharmacokinetic parameters of 3CM obtained were as follows: Tmax = 28.9 ± 1.1 min, Cmax = 0.57 ± 0.02 µg/ml, AUCtotal = 66.3 ± 1.0 µg min/ml, Kel = 0.018 ± 0.002 min-1, and T1/2el = 39.4 ± 3.9 min (n = 3). The long elimination half-life and low Cmax indicated that 3CM was extensively distributed in the deep and very deep tissues. In addition, 3CM demonstrated slower onset of action and longer elimination time from the body compared to ASA. Thus this new compound is a potential candidate to be developed as a new drug.

Keywords: 2-(3-(chloromethyl)benzoyloxy)benzoic acid; pharmacokinetics; rat; HPLC-DAD.


1. Needs, C.J., Brooks, P.M.. Clinical Pharmacokinetics of the Salicylates, Clinical Pharmacokinetics 1985; 10(2):164-177.

2. Levy, G.. Clinical Pharmacokinetics of Aspirin, Pediatrics 1978; 62(5Pt 2 Suppl):867-72.

3. Fu, C.J., Melethil, S., Mason, W.D.. The Pharmacokinetics of Aspirin in Rats and the Effect of Buffer, Journal of Pharmacokinetics and Biopharmaceutics 1991; 19(2):157–173.

4. Nagelschmitz, J., Blunck, M., Kraetzschmar, J., Ludwig, M., Wensing, G., Hohlfeld, T.. Pharmacokinetics and Pharmacodynamics of Acetylsalicylic Acid After Intravenous and Oral Administration to Healthy Volunteers, Clinical Pharmacology 2014; 6:51-59.

5. Byod, E.M.. The Acute Oral Toxicity of Acetylsalicylic Acid, Toxicology and Applied Pharmacology 1959; 1(3):229-239.

6. Roderick, P.J., Wilkes, H.C., Meade, T.W.. The Gastrointestinal Toxicity of Aspirin: an Overview of Randomised Controlled Trials, British Journal Clinical Pharmacology 1993; 35(3):219-226.

7. Caroline, Foe, K., Esar, S.Y., Retnowati, E., Soewandi, A., Wihadmadyatami, H., Widharna, R.M., Tamayanti, W.D., Kasih, E., Tjahjono, Y.. Evaluation of Analgesic and Antiplatelet Activity of 2-((3-(Chloromethyl)benzoyloxy)Benzoic Acid, unpublished result 2018.

8. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM), Bioanalytical Method Validation 2018.

9. Melo, A., Almeida, H.L., Ferreira, C., Sousa, N., Pego, J.M.. Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior. Front.Behav.Neurosci. 2016; 10.

10. Wientjes, M.G., Levy, G.. Nonlinear Pharmacokinetics of Aspirin in Rats, Journal of Pharmacology and Experimental Therapeutics 1988; 245(3):809-815.
13 Views | Downloads
How to Cite
Caroline, Sie, N., Foe, K., Esar, S. Y., & Jessica, M. A. (2019). Characterization of pharmacokinetics of 2-(3-(chloromethyl)benzoyloxy)benzoic acid in rats . International Journal of Applied Pharmaceutics, 11(5). Retrieved from
Original Article(s)