Simultaneous Measurement of Sirolimus and Everolimus in Whole Blood by HPLC with Ultraviolet Detection

[摘要] The macrolide immunosuppressants sirolimus (Rapamycin; SRL) and its 40- O -(2-hydroxyethyl) derivative everolimus (Certican®; SDZ-RAD) are approved immunosuppressive agents for organ transplantation, but there is evidence that they can interfere with co-medications, including other immunosuppressive agents (1).SRL and SDZ-RAD are metabolized in humans by the hepatic and intestinal cytochrome P450 3A subfamily (2)(3), which also metabolizes many other agents. Both have the same mechanism of action but differ in their half-lives and treatment regimes with co-medications. Because of their narrow therapeutic spectra, the clinical application of SRL and SDZ-RAD, like other immunosuppressants, is complicated by substantial intra- and interindividual variations in drug absorption, distribution, metabolism, and elimination (4)(5)(6). Their concentrations must be carefully monitored in posttransplantation regimens, and dosage adjustment to reduce the risk of toxicity and rejection depends on the analytical method used for monitoring (7)(8)(9).Several HPLC methods with ultraviolet (UV) detection or mass spectrometry (MS) are available for measurement of SRL and SDZ-RAD individually (10)(11)(12)(13)(14)(15)(16), and liquid chromatography (LC) methods using MS or tandem MS allow simultaneous measurement of these compounds in combination with other immunosuppressants (17)(18)(19)(20)(21)(22). The purported advantage of LC-MS methods over LC-UV methods is the ability to monitor multiple drugs within the same analytical run. As the number of monitored compounds increases, however, instrument dwell time or the number of data points acquired for each mass transition may decrease and negatively affect the limit of quantification or precision (6)(23). Furthermore, these methods are expensive and not readily available in most laboratories.The presented reversed-phase HPLC-UV method for the simultaneous measurement of SRL and SDZ-RAD in whole blood …

[学科分类] 过敏症与临床免疫学