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

Abstract

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.

A Comprehensive Approach to Compatibility Testing Using Chromatographic, Thermal and Spectroscopic Techniques: Evaluation of Potential for a Monolayer Fixed-Dose Combination of 6-Mercaptopurine and Folic Acid

“…Dissolution was carried out for 60 min, with sampling intervals every 15 min. Five milliliters of the medium were drawn, filtered and analyzed using a modified previously reported method [ 34 ]; after which, the drawn volume was replenished using fresh medium. All tests were done in triplicate.…”

A chromatographic approach to development of 5-aminosalicylate/folic acid fixed-dose combinations for treatment of Crohn’s disease and ulcerative colitis

“…The same HPLC conditions, mobile phases and calculation approaches were used for evaluation of IAM affinity, as in determining hydrophobicity with the RP-HPLC column. Binding percentage of analytes to plasma proteins (PPB HSA and PPB AGP ) was determined using the procedure described in our previously published paper 21 .…”

“…Binding percentage of analytes to plasma proteins (PPB HSA and PPB AGP ) was determined using the procedure described in our previously published paper 21 .…”

UV/Vis absorption spectroelectrochemistry of folic acid

“…FA has been studied and quantified with different analytical techniques such as photoluminescence [41][42][43], UV/ Vis absorption spectroscopy [44,45], electrochemistry [39,[46][47][48][49], HPLC [50,51], or HPLC-MS [52,53]. Some of these techniques require complex and long sample pretreatments; others imply the modification of the surface used to determine this molecule such as in electrochemistry.…”