Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods

With the increase in the number of medicines patients have to take, there has been a rapid rise of fixed-dose combinations (FDCs) in the last two decades. Prior to FDC development, pharmacokinetic properties of active pharmaceutical ingredients (APIs) have to be evaluated, as well as methods for their determination developed. So as to increase patient compliance in inflammatory bowel disease, three novel FDCs of thiopurine immunosuppressants and folic acid are proposed; physico-chemical and pharmacokinetic properties such as hydrophobicity, lipophilicity and plasma protein binding of all APIs are evaluated. Moreover, experimental results of different properties are compared to those computed by various on-line prediction platforms so as to evaluate the viability of the in silico approach. A simultaneous method for their determination is developed, optimized, validated and applied to commercial tablet formulations. The method has shown to be fast, selective, accurate and precise, showing potential for reliable determination of API content in proposed FDCs during its development.