Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma

Abstract

Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.

A sensitive bioanalytical ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method for the simultaneous quantitation of lactone and carboxylate forms of topotecan in plasma and vitreous

“…The standard solutions (50 µg/mL) were prepared by dissolving TPT in a 5 mM ammonium acetate buffer with different pH values (3.0, 4.5, 5.5, 6.5, 7.4, and 10.0). Since methanol was often used as a stabilizing agent [16,17,24,25] the TPT standard solution with 50% methanol content was also tested. The solutions were kept at 8 • C. The samples were analyzed at different times (0, 2, 4, and 25 h) after their preparation.…”

“…The determination of the total TPT (lactone plus carboxylate forms) in human plasma was conducted on Zorbax SB‐C18 Stable Bond column with a mobile phase consisting of methanol/0.1 M hexane‐1‐sulfonic acid in methanol/0.01 M N , N , N ', N '‐tetramethylethylenediamine in distilled water pH 6.0 (25:10:65, v / v / v ) [23]. The separation system consisted of Nova‐pack C18 column in combination with a binary mobile phase 85:15 ( v / v ) acetonitrile:triethylamine buffer, pH 5.5 was used to study ocular TPT pharmacokinetics but TPT lactone and then total TPT by conversion to acidic pH were determined [24].…”