Abstract
A simple, precise, and accurate reversed-phase ultra-performance liquid chromatographic (UPLC) method was developed and validated for the determination of a mycophenolic acid-curcumin (MPA-CUR) conjugate in buffer solutions. Chromatographic separation was performed on a C18 column (2.1 × 50 mm id, 1.7 µm) with a gradient elution system of water and acetonitrile, each containing 0.1% formic acid, at a flow rate of 0.6 mL/min. The column temperature was controlled at 33 °C. The compounds were detected simultaneously at the maximum wavelengths of mycophenolic acid (MPA), 254 nm, and curcumin (CUR), or MPA-CUR, at 420 nm. The developed method was validated according to the ICH Q2(R1) guidelines. The linear calibration curves of the assay ranged from 0.10 to 25 μg/mL (r2 ≥ 0.995, 1/x2 weighting factor), with a limit of detection and a limit of quantitation of 0.04 and 0.10 μg/mL, respectively. The accuracy and precision of the developed method were 98.4–101.6%, with %CV < 2.53%. The main impurities from the specificity test were found to be MPA and CUR. Other validation parameters, including robustness and solution stability, were acceptable under the validation criteria. Forced degradation studies were conducted under hydrolytic (acidic and alkaline), oxidative, thermal, and photolytic stress conditions. MPA-CUR was well separated from MPA, CUR, and other unknown degradation products. The validated method was successfully applied in chemical kinetic studies of MPA-CUR in different buffer solutions.
Highlights
The ultra-performance liquid chromatographic (UPLC) analytical method was developed to quantify mycophenolic acid-curcumin (MPA-CUR) in the samples used in the chemical kinetic study, which is an important topic in the physicochemical analysis of new substances
Stability-indicating UPLC method was developed for the quantitative analysis of mycophenolic acid (MPA)-CUR
The forced degradation study demonstrated that the MPA-CUR conjugate was highly labile to basic hydrolysis and photolysis
Summary
A mutual prodrug strategy derives several benefits from having two active compounds in one molecule [1]. We recently synthesized a novel mycophenolic acid-curcumin (MPA-CUR) conjugate as a prodrug of mycophenolic acid (MPA) and curcumin (CUR). The bioavailable fraction (BF) of MPA-CUR across Caco-2 cells showed better anti-psoriatic and anti-inflammatory effects than that of CUR in a TNF-α-induced HaCaT cell model [2], suggesting MPA-CUR as a potential candidate for psoriasis treatment [2]. Because MPA-CUR requires bioconversion, giving parent molecules to exert anti-psoriatic activity, chemical kinetic studies of MPA-CUR are useful in determining the stability of MPA-CUR under physiological conditions. Prodrug stability is usually carried out in buffer
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