Simple and sensitive high performance liquid chromatographic method for the simultaneous quantitation of the lactone and carboxylate forms of topotecan in human plasma

Involvement of P-glycoprotein, Multidrug Resistance Protein 2 and Breast Cancer Resistance Protein in the Transport of Belotecan and Topotecan in Caco-2 and MDCKII Cells

“…The concentrations of belotecan and topotecan in the samples were determined using modified reverse-phase HPLC (28,29). Briefly, a 50-μl aliquot of the sample was spiked with 50 μl of the internal standard acetonitrile solution, 50 μl acetonitrile and 50 μl of 7% (w/v) perchloric acid, and mixed.…”

“…For the analysis of transport study samples, 100 μl of sample were acidified with 200 μl of phosphoric acid (30%, w/v). The addition of acids (perchloric acid for plasma samples and phosphoric acid for transport samples) was to ensure the conversion of each drug into its respective lactone (29). HPLC was performed using a C 18 column (XTerra TM , 250 mm× 4.6 mm, 5 μm, Waters).…”

Determination of topotecan in human and mouse plasma and in mouse tissue homogenates by reversed‐phase high‐performance liquid chromatography

“…Based on these results we decided to utilize an analytical assay in which total topotecan levels were measured. High-performance liquid chromatography (HPLC) assays have been described for the determination of topotecan in human plasma (Beijnen et al, 1990;Bai et al, 2003;Rosing et al, 1999;Loos et al, 1996;Vali et al, 2005), urine and feces (Rosing et al, 1999;Loos et al, 1996) and in mouse plasma (Chen and Balthasar, 2005), but not in tissues. Based on an HPLC assay developed previously in our group (Beijnen et al, 1990;Rosing et al, 1995) we here present a reversed-phase HPLC method with comprehensive validation for the analysis of total topotecan (lactone and carboxylate forms) in human and mouse plasma and in a range of mouse tissues.…”

Antineoplastic drugs and their analysis: a state of the art review

“…Several studies have succeeded in resolving the lactone forms and carboxylate forms by ion-pair chromatography to increase retention of the carboxylate forms. [377][378][379][380] In the case of irinotecan analysis, carboxylesterase inactivation was accomplished by the immediate addition of sodium dodecyl sulfate (SDS) 372 Podophyllotoxins extracted from the plant roots of the podophyllum family are considered to be highly toxic molecules, even though they were used as medicinal remedies centuries ago thanks to their antimitotic action. In the '50s, a series of podophyllotoxin derivatives were synthesized and studied in the hope of finding a molecule that retained its anticancer action, but with less toxicity.…”