Choline Salicylate Analysis: Chemical Stability and Degradation Product Identification

Abstract

Choline salicylate (CS) as a derivative of acetylsalicylic acid is commonly used in different drug forms. In medicine, it is applied topically to inflammation of the oral cavity mucosa and in laryngology. However, this substance in the form of an ionic liquid has not been investigated enough. There are no literature studies on stability tests constituting a stage of pre-formulation research. HPLC (Nucleosil C18, 4.6 × 150 mm, 5 μm; methanol-water-acetic acid 60:40:1, 230 nm or 270 nm) and UV (276 nm) methods for the determination of CS in 2% (g/mL) aqueous solutions were developed. Under stress conditions, CS susceptibility to hydrolytic degradation in aqueous medium, hydrochloric acid, sodium hydroxide, and hydrogen peroxide, and the effect of light on the stability of CS solutions were studied with HPLC analysis. The degradation degree of CS and the purity of the solutions were also tested. Choline salicylate has been qualified as practically stable in neutral and acid media, stable in an alkaline medium, very stable in an oxidizing environment, and photolabile in solution. The HPLC-MS/MS method was used to identify 2,3- and 2,5-dihydroxybenzoic acids as degradation products of CS under the tested conditions.

Novel Formulation of Eye Drops Containing Choline Salicylate and Hyaluronic Acid: Stability, Permeability, and Cytotoxicity Studies Using Alternative Ex Vivo and In Vitro Models

“…The pharmacopeial method of salicylic acid purity analysis was used to assess the chemical purity of the eye drops [ 38 ]. Of the additional peaks (2.8–3.6 min—P1, and 5.8–6.4 min—P2) observed in the chromatograms of CS (2%) and HA (0.4%) ( Figure 4 ), the P2 peak was identified in earlier studies as phenol—an impurity of the raw material [ 39 ] that cannot exceed a level of 0.001% in drops.…”

“…Liquid chromatography with UV detection (HPLC-UV) was used to determine CS in eye drops and to analyze the chemical purity of the drops. The device was a Shimadzu LC-10AT VP liquid chromatograph with SPD-10A VP UV–vis detector (Shimadzu, Kyoto, Japan), Rheodyne 7120 with 20 µL dosing loop; stationary phase: Nucleosil 100 C18, 4.6 mm × 150 mm, 5 µm (MZ Analytical); mobile phase: methanol-water-acetic acid (60:40:1, v / v / v ), flow rate 1.0 mL/min for the assay and 0.5 mL/min for the purity analysis; detection at 230 nm or 270 nm for determination and purity analysis, respectively [ 39 ]. Detailed validation information was published in our previous paper [ 39 ].…”

“…Dwell time was set at 50.0 ms. The HPLC-MS/MS system was controlled, and the data acquisition and processing were conducted using Analyst Software version 1.6.3 (Sciex, Framingham, MA, USA) [ 39 ]. More validation information was published in our previous paper [ 39 ].…”

“…UV method: 0.2 mL of the eye drops was supplemented with water (or PBS in the permeation study) to 100.0 mL. The CS content was calculated using the parameters of the standard curve: y = (1.34 ± 0.01) 10 −2 x [ 39 ] or y = (1.38 ± 0.01) 10 −2 x for PBS buffer as solvent (x—CS concentration in µg/mL; y—absorbance at 296 nm). The parameters of the CS standard curve in PBS solution were determined in the range of 5.5–88.6 µg/mL [ 26 ].…”

“…The parameters of the CS standard curve in PBS solution were determined in the range of 5.5–88.6 µg/mL [ 26 ]. The validation and revalidation information can be found in our previous papers [ 26 , 39 ].…”