Liquid chromatographic method for the determination of sirolimus in blood using electrochemical detection

Abstract

Therapeutic drug monitoring of sirolimus (rapamycin) is important for immunosuppressive therapy in solid organ transplantation. We have developed a simple and reliable method for determining blood concentrations of sirolimus using reversed-phase HPLC with electrochemical detection (ECD). The E(2) potential was set at +900 mV. The potential of guard cell was set at +950 mV and that of the E(1) cell at +400 mV. The method was linear for a concentration range of 1-50 ng/mL when 0.5 mL blood was used. The correlation coefficients of all standard curves were greater than or equal to 0.999. The limit of detection was 0.5 ng/mL. The inter-assay precision ranged from 3.22 to 7.48%, and the coefficient of variation (CV) for a quality control sample at 10 ng/mL was 7.48% with a bias of 8.4% from the target value. The intra-assay precision ranged from 0.72 to 3.71%, and the CV for a quality control sample at 10 ng/mL was 0.72% with a bias of 6.8% from the target value. In a solid organ transplant recipient, trough concentrations of sirolimus were well within the analytic range of the HPLC/ECD procedure. The method described here is suitable for management of sirolimus therapy in solid organ transplantation.

Development of a validated high‐throughput LC‐ESI‐MS method for determination of sirolimus on dried blood spots

“…At present, two methods of measuring drug concentrations are available: the reference method is high-performance liquid chromatography (HPLC) with ultraviolet (UV) or mass spectrometry (MS) detection and a second technique is an enzyme immunoassay using micro particles coated with anti-sirolimus antibodies (MEIA) (Zhang et al, 2007;Buchberger et al, 2004;Kirchner et al, 1999;Taylor and Johnson, 1998;Morris et al, 2006;Mochizuki et al, 2009;Koal et al, 2004;Christiansa et al, 2000;Cattaneo et al, 2002). The reported chromatographic methods for measuring sirolimus blood levels in patients with organ transplants are time-consuming when large numbers of samples have to be processed.…”

Development of Simple and Robust RP-HPLC Method for Determination of Everolimus and its Impurities in Oral Solid Dosage Form

“…For the estimation of solo everolimus, some analytical methods are reported, such as HPLC with UV detection [7,8], high-throughput HPLC technique [9], Liquid chromatographic method [10], LC and LC/MS approach [1,11], high-throughput LC-ESI-MS [12], HPLC with electrospray tandem mass spectrometry [13] and HPLC technique [14,15]. However, the reported analytical methods measured only solo everolimus using different detectors.…”

Production of a sensitive antibody against sirolimus for chemiluminescence immunoassay potential in its therapeutic drug monitoring

“…The TDM of sirolimus has been accomplished through highperformance liquid chromatography (HPLC) with either tandem mass spectrometry (MS) detection [9][10][11][12] or electrochemical detection. 13 These methods are generally accurate and sensitive but are also laborious, time consuming and expensive. Therefore, it is necessary to develop a novel method which can rapidly realise the TDM of sirolimus whilst maintaining cost effectiveness.…”