Research Article RP-HPLC Method Development and Validation of Synthesized Codrug in Combination with Indomethacin, Paracetamol, and Famotidine Mohyeddin Assali , Murad Abualhasan , Nihal Zohud , and Noura Ghazal Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, State of Palestine Correspondence should be addressed to Mohyeddin Assali; m.d.assali@najah.edu Received 24 March 2020; Revised 31 May 2020; Accepted 11 June 2020; Published 1 July 2020 Academic Editor: Antonio V. Herrera-Herrera Copyright © 2020 Mohyeddin Assali et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Indomethacin is considered a potent nonsteroidal anti-inflammatory drug that could be combined with Paracetamol to have superior and synergist activity to manage pain and inflammation. To reduce the gastric side effect, they could be combined with Famotidine. Methodology. A codrug of Indomethacin and Paracetamol was synthesized and combined in solution with Famotidine. e quantification of the pharmaceutically active ingredients is pivotal in the development of pharmaceutical formulations. erefore, a novel reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated according to the International Council for Harmonization (ICH) Q2R1 guidelines. A reverse phase C18 column with a mobile phase acetonitrile: sodium acetate buffer 60 : 40 at a flow rate of 1.4 mL/min and pH 5 was utilized. Results. e developed method showed good separation of the four tested drugs with a linear range of 0.01–0.1 mg/mL (R 2 > 0.99). e LODs for FAM, PAR, IND, and codrug were 3.076 × 10 −9 , 3.868 × 10 −10 , 1.066 × 10 −9 , and 4.402 × 10 −9 mg/mL respectively. While the LOQs were 9.322 × 10 −9 , 1.172 × 10 −10 , 3.232 × 10 −9 , and 1.334 × 10 −8 mg/mL, respectively. Furthermore, the method was precise, accurate, selective, and robust with values of relative standard deviation (RSD) less than 2%. Moreover, the developed method was applied to study the in vitro hydrolysis and conversion of codrug into Indomethacin and Paracetamol. Conclusion. e codrug of Indomethacin and Paracetamol was successfully synthesized for the first time. Moreover, the developed analytical method, to our knowledge, is the first of its kind to simultaneously quantify four solutions containing the following active ingredients of codrug, Indomethacin, Paracetamol, and Famotidine mixture with added pharmaceutical inactive ingredients in one HPLC run. 1. Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most consumed and prescribed drugs for both pain and inflammation worldwide [1]. eir blockage of prosta- glandin synthesis by inhibiting cyclooxygenase (COX) is responsible for both the desired anti-inflammatory effects and the undesired gastrointestinal effects [2–4]. Based on COX selectivity, NSAIDs are divided into two families: nonselective NSAIDs that block both cyclooxygenase I & II and selective cyclooxygenase II inhibitors [5–7]. Indomethacin (IND) is an example of a potent non- selective COX inhibitor that showed efficient analgesia with antipyretic and anti-inflammatory activities [8]. It is classified as an indole-acetic acid derivative according to the NSAIDs chemical classification with the chemical name of 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-ace- tic acid [9]. It is a poorly soluble class II compound with a half-life of 4-5 h [10, 11]. It is utilized to treat rheumatoid diseases by elevating the inflammation. Moreover, it can decrease the risk of colon cancer by providing chemo- protective effects against tumors [12, 13]. Like other NSAIDs, it appeared to have gastrointestinal, renal, and other side effects [14]. e gastric side effect could be re- versed by the administration of Famotidine (FAM), which is a competitive histamine H2-receptor antagonist that Hindawi International Journal of Analytical Chemistry Volume 2020, Article ID 1894907, 9 pages https://doi.org/10.1155/2020/1894907