A validated HPLC-MS/MS method for determination of simmitecan and its metabolite chimmitecan in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumor.
J Sep Sci
; 44(21): 3959-3966, 2021 Nov.
Article
em En
| MEDLINE
| ID: mdl-34472219
ABSTRACT
Simmitecan is a new ester anticancer prodrug which can exert the antiproliferation activity through its active metabolite, chimmitecan. In the current study, a simple and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of simmitecan and chimmitecan in human plasma. Both irinotecan and 7-ethyl-10-hydroxycamptothecin were used as the internal standards. Plasma samples were protein precipitated by acetonitrile (0.2% formic acid, v/v) and processed samples were chromatographed on a Hypersil GOLDTM C18 column (100 × 4.6 mm, i.d. 3.0 µm) with acetonitrile and 10 mM ammonium acetate (0.1% formic acid, v/v) as the mobile phase. The calibration curves showed good linearity (R ≥ 0.99) over the concentration range of 1-500 ng/mL and 0.25-125 ng/mL for simmitecan and chimmitecan, respectively. Intra- and inter-run precisions (CV%) were ≤10.2% for simmitecan and ≤12.1% for chimmitecan. The accuracies were 99.4-103.5% for simmitecan and 95.4-103.5% for chimmitecan. This method was further successfully applied to a pharmacokinetic study of simmitecan in Chinese advanced solid cancer patients after administration of simmitecan hydrochloride injection.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Camptotecina
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Cromatografia Líquida de Alta Pressão
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Espectrometria de Massas em Tandem
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Sep Sci
Ano de publicação:
2021
Tipo de documento:
Article