title: A simple and sensitive gas chromatography method for determination of isosorbide dinitrate and its metabolites in human plasma: application to pharmacokinetics study on oral spray.
abstract: A sensitive method for the simultaneous determination of isosorbide dinitrate (ISDN) and its mononitrate metabolites, isosorbide 2-mononitrate and isosorbide 5-mononitrate (IS-2-MN and IS-5-MN), in human plasma was developed using capillary gas chromatography with electron-capture detection, whereas 1,2,4-butanetriol trinitrate was used as internal standard. The analytes were extracted with a simple liquid-liquid extraction from plasma and separated on a DB-1 column. The results of method validation demonstrated that the calibration curves were linear in range of 2-60 ng/mL for ISDN and IS-5-MN, 1-20 ng/mL for IS-2-MN, respectively. The precision (RSD%) was less than 15%, and the lower limit of quantitation was identifiable and reproducible at 2 ng/mL for ISDN and IS-5-MN, 1 ng/mL for IS-2-MN. The analytes in plasma were stable after being stored for more than 30 days and after 2 freeze-thaw cycles (-20 to 25°C). And then this method was successfully applied to a pharmacokinetic investigation on isosorbide dinitrate oral spray in healthy volunteers.
authors.affiliation: School of Pharmaceutical Sciences of Shandong University, Shandong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China.
authors.forename: C
authors.initials: C
authors.lastname: Wei
authors.affiliation: School of Pharmaceutical Sciences of Shandong University, Shandong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China.
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China.
authors.forename: G
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China.
authors.forename: R
authors.initials: R
authors.lastname: Guo
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004355:Drug Stability; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male
chemical_list: C030398:isosorbide-2-mononitrate; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate