UPLC method development and validation for the estimation of sulbactam and durlobactum in pharmaceutical dosage form

Title : UPLC method development and validation for the estimation of sulbactam and durlobactum in pharmaceutical dosage form

Abstract:

Infectious diseases especially associated with multidrug resistant pathogens in critically ill patients is an area of global research and concern for healthcare professionals across both private and public sector. Sulbactam and Durlobactam have been approved as a combination drug, called Xacdura, recently for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) caused by Acinetobacter baumannii-calcoaceticus complex and is commercially available currently only in the US and China. With 1 million cases of drug-resistant Acinetobacter infections seen globally year-on-year leading to potentially about 300,000 deaths, we expect rapid investments in the development of follow-on drugs, even though the primary patents expire between 2033-2035. Currently there is no pharmacopeia method for this combination which can aid in quantification or purity testing to aid these pharmaceutical development efforts. Accordingly, we have developed an ultra-performance liquid chromatography (UPLC) method for the simultaneous estimation of Sulbactam and Durlobactum. The best chromatographic separation was obtained when the HSSC18 column (1.7μm; 2.1 x 100mm) was used with 0.01N KH₂P0₄ : Methanol in 70:30 v/v ratio as mobile phase at an injection volume of 3μL, and run rate of 0.3mL/min. Sulbactam and Durlobactam eluted at 1.77 and 1.33 minutes respectively. The described method shows high precision, sensitivity, resolution, accuracy, linearity and robustness as well as reliability. The method was specific as none of the known or unknown impurities expected during the degradation experiments, conducted across different conditions, were seen to be eluted during the same window as the chosen drugs. The described method is expected to accelerate the development and commercialization of the formulations of these drugs with higher efficiency, lower cost and faster run rate.

Audience Take Away Notes:

• Given the importance of the antibiotic resistance and the need for these drugs globally, the audience gets to understand the detailed validated methodology to simultaneously quantify the parent drugs and detect any impurities accelerating the drug registration and approval in many countries
• Deployment of QbD approach to simultaneously detect two drugs yielding a new scalable and economic UPLC method
• The diverse parameters, per ICH guidelines, that get validated before deploying any analytical chemistry method in drug discovery and development

Biography:

Rayhan S. Shanavas is a senior at Oakridge International School, UNICEF Ambassador of his school, and the co-founder of The Synapse Foundation. He is committed to building a more equitable society by understanding healthcare disparities and innovating with other change leaders. Access to pharmaceutical drugs is one such critical healthcare challenge that he is focussing on by evaluating drug development and approval value chain and bottlenecks that need to be solved for. He has worked with senior authors on this project by evaluating the therapeutic landscape, available methods, analyzing and validating the data from optimized methods against the required specifications.