Journal of pharmaceutical and biomedical analysis
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J Pharm Biomed Anal · Mar 2013
Controlled Clinical TrialAbsolute bioavailability studies of a new oral topotecan formulation in Chinese patients using UHPLC-MS/MS.
Xinze(®) is a new capsule formulation of topotecan being made in China which is similar to Hycamtin(®), the currently available oral formulation approved in 2007 for the treatment of relapsed small cell lung cancer (SCLC). As topotecan bioavailability and pharmacokinetic data for Chinese patients is limited, the aim of the study was to assess the absolute bioavailability and pharmacokinetics of Xinze(®) in Chinese patients with SCLC treated intravenously (i.v.) with 1.5mg/m(2)/d topotecan (Hycamtin(®)) on day 1 and treated orally with 1.5mg/m(2)/d topotecan on day 2. An ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of total topotecan (lactone and carboxylate forms) and of topotecan in the lactone form in human plasma samples. ⋯ The quantification limits were 0.5ng/mL for total topotecan and 0.1ng/mL for topotecan in the lactone form. The mean absolute bioavailability of total topotecan and topotecan in the lactone form was 42.24±12.9% and 47.18±16.9%, respectively, values which illustrate good systemic exposure. The presented results demonstrated this method can be a sensitive and efficient tool for bioavailability studies of topotecan.
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J Pharm Biomed Anal · Mar 2013
Simultaneous determination and pharmacokinetic study of stachydrine and leonurine in rat plasma after oral administration of Herba Leonuri extract by LC-MS/MS.
A simple, sensitive and specific method was developed for simultaneous determination of stachydrine and leonurine in rat plasma using diphenhydramine as an internal standard (IS). The separation was performed on an Agilent ZORBAX Eclipse XDB-C(18) column (150mm×4.6mm, i.d., 5μm) at a flow rate of 0.6mL/min, and the mixture of methanol-water containing 0.1% formic acid was used as the mobile phase. ⋯ After single oral administration of 14.5g/kg Herba Leonuri extract, C(max) of stachydrine and leonurine in rat plasma were respectively 1608±267 and 43.3±8.2ng/mL, while T(max) values were respectively 0.75±0.27 and 0.83±0.26h. The results demonstrated that the present LC-MS/MS method was sensitive enough for pharmacokinetic study of stachydrine and leonurine following oral administration of Herba Leonuri extract.
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J Pharm Biomed Anal · Mar 2013
A bioassay for the detection of neutralizing antibodies against the α-melanocyte stimulating hormone analog afamelanotide in patients with erythropoietic protoporphyria.
The tridecapeptide afamelanotide (Scenesse®) is a congener of α-melanocyte stimulating hormone (α-MSH). Upon binding to the melanocortin 1 receptor (MC1R) on the surface of pigment cells of the skin, the melanocytes, α-MSH or afamelanotide trigger the synthesis of cAMP, which stimulates the synthesis of melanin and therefore induces skin tanning. In a recent trial, afamelanotide administered as controlled release implants protected erythropoietic protoporphyria (EPP) patients from sunlight induced phototoxic skin reactions. ⋯ Using forskolin as a hormone-independent stimulator of cAMP formation, we excluded an unspecific interference of EPP sera with cAMP formation. We conclude that afamelanotide even after prolonged application to EPP patients did not elicit neutralizing antibodies. Further, the low titer immunoreactivity observed in sera of some drug-naïve individuals had no effect on the biological activity of afamelanotide.