Determination of Mesalamine Related Impurities from Drug Product by Reversed Phase Validated UPLC Method

Abstract

In the present study gradient reversed-phase UPLC method was developed for simultaneous determination and separation of impurities and degradation products from drug product. The chromatographic separation was performed on acquity UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm) using gradient elution. Other UPLC parameters which were optimised are flow rate, 0.7 mL/min; detection wavelength, 220 nm; column oven temperature, 40°C and injection volume 7 µL. Stability indicating capability was established by forced degradation experiments and separation of known degradation products. The method was validated as per International Conference on Harmonization (ICH) guideline. For all impurities and mesalamine, LOQ (limit of quantification) value was found precise with RSD (related standard daviation) of less than 2.0%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was successfully applied for quantification of impurities and degradation products in mesalamine delayed-release formulation. The same method can also be used for determination of related substances from mesalamine drug substance.

Advanced Real‐Time Process Analytics for Multistep Synthesis in Continuous Flow**

“…Based on a literature-known UHPLC method for the separation of 5-ASA from six potential impurities within the final drug product, [1] we initiated method development with the evaluation of an aq. phosphate buffer/MeOH system.…”

“…phosphate buffer/MeOH system. With a total analysis time of 15 min and a different impurity profile, [1] the main objectives were adapting this method for the main analytes occurring within the three-step synthesis, while simultaneously minimizing the analysis time.…”

“…Inline NMR reaction monitoring was accomplished by recording 1 H spectra using a low field benchtop 43.795 MHz NMR spectrometer (Magritek, Spinsolve Ultra 43 MHz). Shims were performed with the flow cell filled with either reaction mixture or an aqueous 0.5 M NaOH solution and referenced to the water peak at 5.00 ppm.…”

“…Continuous flow processing is now widely accepted as a disruptive technology in the synthesis of active pharmaceutical ingredients (APIs) as well as other fine and commodity chemicals. 1 This processing method has proven particularly useful in multiple synthetic transformations in sequence, known as multistep flow synthesis. This approach has been utilized to synthesize a number of APIs, often providing significant improvements in processing time, safety and yield.…”

Different Spectrophotometric and TLC-Densitometric Methods for Determination of Mesalazine in Presence of Its Two Toxic Impurities

“…[11][12][13][14][15] The drug was also determined by different UV-spectrophotometric, 16) and Vireodt's method. 17) Spectrofluorimetric, 18,19) TLC, 20,21) HPLC, [22][23][24][25] ultra performance liquid chromatography (UPLC) 26,27) and LC-MS 28) were reported for analysis of ME either in single or in combination with other drugs. Only one HPTLC method was published for determination of ME and its degradation products that depended on using toluene-methanol-ethyl acetate (6.5 : 2.5 : 1, v/v/v) as a developing system and scanning at 244 nm.…”