A sensitive and rapid liquid chromatography tandem mass spectrometry method for quantitative determination of 7-ethyl-10-hydroxycamptothecin (SN-38) in human plasma containing liposome-based SN-38 (LE-SN38).

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Khan S, Ahmad A, Ahmad I

Biomed Chromatogr. 2003 Dec;17(8):493-9.

PubMed ID

14648604 [ View in PubMed

]

Abstract

7-Ethyl-10-hydroxycamptothecin (SN-38) is an active metabolite of Irinotecan (CPT-11), an anticancer pro-drug. To support clinical pharmacokinetic studies for liposome based formulation of SN-38 (LE-SN38) in cancer patients, a rapid, simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of total SN-38 in human plasma. Sample preparation was carried out by one-step protein precipitation using cold acetonitrile with 0.5% acetic acid (v/v). Camptothecin was used as an internal standard (IS). Chromatographic separation of SN-38 and IS was achieved using a Synergi Hydro-RP column (C(18), 50 x 2 mm, 4 micro m), with a gradient elution of acetonitrile and 0.1% acetic acid. After ionization in electrospray source (positive ions), the acquisition was performed in the multiple reactions monitoring mode. Quantitation was accomplished using the precursor-->product ion combinations of m/z 393.1-->349.2 for SN-38 and 349.1-->305.1 for IS. The quantification limit of 0.05 ng/mL was achieved by using much lower volume (0.2 mL) of plasma and in the presence of LE-SN38. The method was validated over the concentration range of 0.05-400 ng/mL. Accuracy was within +/-12% of nominal at all concentration levels. Inter-day and intra-day precisions expressed as percentage coefficient of variation (%CVs) for quality control (QC) samples were less than 14 and 5%, respectively.

DrugBank Data that Cites this Article

Drugs: SN-38