Characterization of Pharmacokinetics of 2-((3-(Chloromethyl)benzoyl)oxy) Benzoic Acid in Rats by Using HPLC-Dad Method

Abstract

Objective: A new compound of salicylic acid derivative, namely 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3CBB), was synthesized to find a compound exhibiting higher analgesic activity and smaller ulcer irritation than acetylsalicylic acid (ASA). Therefore, this study aimed to investigate the pharmacokinetics of this new compound in rats, following a single dose oral administration of 3CBB (45 mg/kg BW).
 Methods: Plasma samples of 9 healthy rats were collected before and up to 3 h after its oral administration, following an 18 h fasting period. Plasma concentrations of 3CBB were determined using a validated HPLC-DAD assay. Pharmacokinetic parameters were determined using the compartment model technique. All experiments were carried out in triplicate.
 Results: The pharmacokinetic parameters of 3CBB 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. The long elimination half-life and low Cmax indicated that 3CBB was extensively distributed in the deep and very deep tissues. This confirmed the unique and special characteristics of a highly lipophilic compound like 3CBB (log P = 3.73).
 Conclusion: 3CBB demonstrated a 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.

Synthesis, Characterization, and Application of 2-((3-(Chloromethyl)-benzoyl)oxy)benzoic Acid: A Review

“…The elimination life constant ( K el ) was 0.018 ± 0.002 min –1 . Based on these findings, 3-CH 2 Cl exerts a slower onset of action and longer elimination time than ASA …”

“…To investigate the 3-CH 2 Cl absorption pattern, the pharmacokinetic studies have been performed in a rat model using high-pressure liquid chromatography diode array detector (HPLC-DAD) method 18 with a single dose of 45 mg/kg body weight (BW). The maximum plasma concentration of 3-CH 2 Cl ( C max ) was 0.57 ± 0.02 μg/mL.…”

“…Based on these findings, 3-CH 2 Cl exerts a slower onset of action and longer elimination time than ASA. 18 …”

Tablet Formulation of 2-((3-(Chloromethyl)benzoyl)oxy)benzoic Acid by Linear and Quadratic Models

“…However, the lipophilic value of 3CH 2 Cl (log P ) is 3.73. 3 While the optimal log P value of the water-soluble compound during tablet formulation is theoretically between 2 and 3, 4 the reported log P value of 3CH 2 Cl indicates the difficulty of solubility in water.…”

“…It indicates the ability of 3CH 2 Cl to distribute and perfuse widely into the very deep interstitial and intracellular parts of the tissue. However, the lipophilic value of 3CH 2 Cl (log P ) is 3.73 . While the optimal log P value of the water-soluble compound during tablet formulation is theoretically between 2 and 3, the reported log P value of 3CH 2 Cl indicates the difficulty of solubility in water.…”