Sirolimus and Ketoconazole are used in organ transplantation regimen and potential metabolic interactions of these drugs
were reported when administered concomitantly. An analytical method based on high-performance liquid chromatography
(HPLC) with photo diode array (PDA) detection was developed for quantification of sirolimus using ketoconazole as
internal standard. Extraction was performed using dichloromethane under nitrogen atmosphere and the separation of
sirolimus and ketoconazole was accomplished by reverse phase chromatography. The mobile phase consists of a
combination of methanol, water and glacial acetic acid at 90:10:0.1% ratios run isocratically through a C18 (250mm ×
4.6mm, 5µm) reverse phase analytical column. The PDA detection was done at 278nm with analytical run time less than 6
min. The average mean recovery was found to be 98.3% for 1, 3, 5, 10µg/ml concentrations. The assay exhibited good
linear relationship. LLOQ was 10ng/ml with 0.84% and 1.28% of accuracy and precision over the concentration range of
0.1-10µg/ml. The method can be successfully applied for estimation of sirolimus from in-vitro elution studies of sirolimus
eluting stents, simultaneous estimation of ketoconazole and sirolimus in therapeutic drug monitoring and other
pharmacokinetic studies
Sirolimus and Ketoconazole are used in organ transplantation regimen and potential metabolic interactions of these drugswere reported when administered concomitantly. An analytical method based on high-performance liquid chromatography(HPLC) with photo diode array (PDA) detection was developed for quantification of sirolimus using ketoconazole asinternal standard. Extraction was performed using dichloromethane under nitrogen atmosphere and the separation ofsirolimus and ketoconazole was accomplished by reverse phase chromatography. The mobile phase consists of acombination of methanol, water and glacial acetic acid at 90:10:0.1% ratios run isocratically through a C18 (250mm ×4.6mm, 5µm) reverse phase analytical column. The PDA detection was done at 278nm with analytical run time less than 6min. The average mean recovery was found to be 98.3% for 1, 3, 5, 10µg/ml concentrations. The assay exhibited goodlinear relationship. LLOQ was 10ng/ml with 0.84% and 1.28% of accuracy and precision over the concentration range of0.1-10µg/ml. The method can be successfully applied for estimation of sirolimus from in-vitro elution studies of sirolimuseluting stents, simultaneous estimation of ketoconazole and sirolimus in therapeutic drug monitoring and otherpharmacokinetic studies
การแปล กรุณารอสักครู่..