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• W2898897022 abstract "Sirolimus is regarded as one of the most effective immunosuppressants receiving extensive attention over the years, for which the ocular application needs further development in clinical keratoplasty. In order to study the transcorneal absorption effect of ophthalmic administration, there was a need to study the pharmacokinetics of drugs in aqueous humor. In this work, a validated and reliable HPLC-ESI-MS/MS method was established to study the pharmacokinetics of sirolimus nanoformulations in rabbit aqueous humor. The analysis conditions were as follows. Ascomycin was chosen as internal standard. After a simple precipitation extraction procedure, the aqueous humor samples were separated on a XBridge C18 column (4.6 mm × 150 mm, 3.5 μm, Waters Co., USA) with a mobile phase comprised of water (0.1% formic acid and 5 mM ammonium formate) and methanol (0.1% formic acid) at the ratio of 10:90 (v/v). The mass analysis was achieved by positive ionization with multiple reaction monitoring (MRM) mode. The highest response ion pairs m/z at 931.5→864.5 were chosen for sirolimus. The validated results showed that the calibration range was 0.3–100.6 ng/mL with r = 0.9997 (n = 6). The R.S.D. values of the intra- and inter-day precision were less than 11% and the average accuracy values were between 94.73%–100.20%. Besides, for reducing the consumption of rabbits and the variation of the data, we designed a consecutive sampling method in pharmacokinetic study, with only seven rabbits consumed for each formulation. In conclusion, the developed analysis method was more reliable and practical than previously reported experiments. Meanwhile, the validated method was successfully applied to study the pharmacokinetics of sirolimus micelle and sirolimus nanosuspension after ophthalmic administration." @default.
• W2898897022 created "2018-11-09" @default.
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• W2898897022 date "2019-02-01" @default.
• W2898897022 modified "2023-09-27" @default.
• W2898897022 title "Pharmacokinetic study of sirolimus ophthalmic formulations by consecutive sampling and liquid chromatography–tandem mass spectrometry" @default.
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• W2898897022 doi "https://doi.org/10.1016/j.jpba.2018.10.051" @default.
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