Stability-indicating HPLC-DAD and TLC-densitometry methods for the quantification of bupivacaine and meloxicam in their co-formulated mixture

• Published in: Microchemical journal Vol. 190; p. 108683
• Main Authors: Bahgat, Eman A., Hashem, Hisham, Saleh, Hanaa, Kamel, Ebraam B., Eissa, Maya S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.07.2023
• Subjects: Bupivacaine; Degradation kinetic; Liquid chromatography; Meloxicam; Stability-indicating; Degradation kinetic; Meloxicam; Stability-indicating; Liquid chromatography; Bupivacaine
• ISSN: 0026-265X; 1095-9149
• DOI: 10.1016/j.microc.2023.108683

[Display omitted] •The first complete stability-indicating methods for simultaneous determination of Bupivacain and Meloxicam.•Isocratic HPLC method with short analytical run and minimal sample consumption for separation of Bupivacain and Meloxicam along with their possible degradation products using the DAD detector.•Degradation kinetics were employed using the HPLC technique, which revealed excellent behaviour from the studied drugs.•A simple and cost-effective HPTLC technique was developed for the first time with noticeable sensitivity.•Comparative statistical analysis was established using interval and probability plots. The implementation of a novel drug formulation necessitates the assessment of its content stability and the designation of appropriate stability monitoring methodologies. Bupivacaine (BVC) and Meloxicam (MLX) were recently authorized under the name Zynrelef® solution. This novel combination was tested for stability under a variety of stress circumstances for the first time in this study. The basic degradation pathway was shown to affect BVC, while the acidic degradation pathway works for MLX. Identification of the acquired degradation products, including BVC impurity F (BVC IMP-F), 1-buytylpiperidine-2- 2carboxylic acid (1-BPC), MLX acid degradation product (MLX-DEG), and MLX impurity B (MLX IMP-B), was carried out using IR and MS spectroscopic techniques. HPTLC and HPLC, two chromatographic-based stability-indicating methods, have been established. The HPTLC method offered efficient separation upon the usage of silica gel 60 F254 as a stationary phase and ethyl acetate/toluene/triethylamine/acetic acid (4:4:2:0.4, v/v/v/v) as a developing system with densitometric recording at 260 nm. The HPLC method was developed by using Zorbax® SB C18 column as a stationary phase and a mobile phase consisting of acetonitrile: methanol: phosphate buffer, pH 6.5 (20:60:20 v/v/v), at a flow rate of 1.5 mL min-1. Quantification of the analytes was performed at 265 nm using a diode array detector. The current research introduced the first stability-indicating methods for the assay of BVC and MLX which were successfully applied for the determination of the cited drugs in their combined pharmaceutical formulation. Moreover, the HPLC method was further extended for studying the degradation kinetics of the two drugs.