MS‐Compatible HPLC Method for Simultaneous Estimation of Ceftriaxone, Pantoprazole, and Ondansetron in Parenteral Formulations and Admixtures

Abstract Concomitant therapies are used for the treatment of serious infection in hospitalized patients. In such treatment, antibiotics had been co‐administered with other drugs like antacids and antiemetic drugs admixed in infusion solution. Such a combination is ceftriaxone sodium, pantoprazole sodium, and ondansetron hydrochloride in parenteral admixture with 5% w/v dextrose injection and 0.9% w/v sodium chloride injection. For evaluation of such a type of combination, a robust mass spectroscopy‐compatible HPLC method for simultaneous quantification had been developed with the aid of Analytical Quality by Design , and the method operable domain region and by evaluating the interaction between critical method parameters/critical method attributes by optimizing the HPLC method using the Box–Behnken design. The optimized method was achieved using a Tragetsil RP‐18 (150 mm × 4.6 mm, 3 µm) column, a gradient of buffer (0.1% trifluoroacetic acid in water), and a solvent mixer (methanol:acetonitrile (50:50, %v/v)) at flow rate of 1 mL/min and detection wavelength at 220 nm. The proposed method was successfully validated according to International Council for Harmonization Q2(R2) guidelines for specificity, accuracy, precision, sensitivity, and linearity over concentrations ranging 100–300 µg/mL for ceftriaxone sodium, 4–12 µg/mL for pantoprazole sodium, 0.4–1.2 µg/mL for ondansetron hydrochloride, respectively. The method exhibits a high degree of accuracy, which was found to be between 98.3% and 101.5% for triplicate at three concentrations. Alongside, limit of quantification level is achieved at 4.01, 0.16, and 0.20 µg/mL for ceftriaxone, pantoprazole, and ondansetron respectively. Analytical Quality by Design based method was successfully applied to estimate ceftriaxone sodium, pantoprazole sodium, and ondansetron hydrochloride in their marketed formulations, such as Monocef, Pantodac, and Emeset respectively as well as in parenteral admixture with 5% w/v dextrose injection and 0.9% w/v sodium chloride injection.