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Drug Res (Stuttg) 2014; 64(02): 73-78
DOI: 10.1055/s-0033-1351286
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Z. Jiang
1   School of Pharmaceutical Sciences of Shandong University, Shandong, China
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
,
C. Wei
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
,
Z. Sun
1   School of Pharmaceutical Sciences of Shandong University, Shandong, China
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
,
J. Guo
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
,
R. Li
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
,
R. Zhang
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
,
G. Yuan
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
,
R. Guo
2   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Shandong, China
› Author Affiliations
Further Information

Publication History

received 29 March 2013

accepted 07 July 2013

Publication Date:
31 July 2013 (online)

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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.

Key words

GC-ECD - isosorbide dinitrate - pharmacokinetics
 

  • References

  • 1 Maddock J, Lewis PA, Woodward A et al. Determination of isosorbide dinitrate and its mononitrate metabolites in human plasma by high-performance liquid chromatography-thermal energy analysis. Journal of Chromatography B 1983; 272: 129-136
    CrossrefPubMedSearch in Google Scholar
  • 2 Yu WC, Ulku-Goff E. Determination of vasodilators and their metabolites in plasma by liquid chromatography with a nitrosyl-specific detector. Anal Chem 1983; 55: 29-32
    CrossrefPubMedSearch in Google Scholar
  • 3 Carlson M, Thompson RD, Snell RP. Determination of Isosorbide Dinitrate in Pharmaceutical Products by HPLC. Journal of Chromatographic Science 1988; 26: 574-578
    CrossrefPubMedSearch in Google Scholar
  • 4 Parham H, Zargar B. Determination of isosorbide dinitrate in arterial plasma, synthetic serum and pharmaceutical formulations by linear sweep voltammetry on a gold electrode. Talanta 2001; 55: 255-262
    CrossrefPubMedSearch in Google Scholar
  • 5 Silva LC, Oliveira LS, Mendes GD et al. Quantification of isosorbide 5-mononitrate in human plasma by liquid chromatography-tandem mass spectrometry using atmospheric pressure photoionization. Journal of Chromatography B: Analytical technologies in the biomedical and life science 2006; 832: 302-306
    PubMedSearch in Google Scholar
  • 6 Chin DA, Prue DG, Michelucci J et al. Quantitative determination of isosorbide dinitrate and two metabolites in plasma. Journal of Pharmaceutical Sciences 1977; 66: 1143-1145
    CrossrefPubMedSearch in Google Scholar
  • 7 Rosseel MT, Bogaert MG. Simultaneous determination of isosorbide dinitrate and its mononitrates in human plasma by capillary column GLC. Journal of Pharmaceutical Sciences 1979; 68: 659-660
    CrossrefPubMedSearch in Google Scholar
  • 8 Spörl-Radun S, Betzien G, Kaufmann B et al. Effects and pharmacokinetics of isosorbide dinitrate in normal man. European Journal of Clinical Pharmacology 1980; 18: 237-244
    CrossrefPubMedSearch in Google Scholar
  • 9 Morrison RA, Fung HL. Determination of the partitioning, stability, and metabolite formation of isosorbide dinitrate in human and rat blood using an improved gas-liquid chromatographic assay. Journal of Chromatography B: Biomedical Sciences and Applications 1984; 308: 153-164
    CrossrefPubMedSearch in Google Scholar
  • 10 Santoni Y, Rolland PH, Cano JP. Determination of isosorbide dinitrate and its mononitrate metabolites in human plasma using extrelut® purification and capillary column gas-liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications 1984; 306: 165-172
    CrossrefPubMedSearch in Google Scholar
  • 11 Straehl P, Galeazzi RL. Isosorbide dinitrate bioavailability, kinetics and metabolism. Clinical pharmacology and therapeutics 1985; 38: 140-149
    PubMedSearch in Google Scholar
  • 12 Michel G, Fay L, Prost M. Determination of isosorbide dinitrate and its metabolites in plasma by gas chromatography on a capillary column with electron-capture detection. Journal of Chromatography 1989; 493: 188-195
    CrossrefPubMedSearch in Google Scholar
  • 13 Booth BP, Bennett BM, Brien JF et al. Assay of glyceryl trinitrate, isosorbide dinitrate, and their metabolites in plasma by large-bore capillary column gas-liquid chromatography. Biopharmaceutics & Drug Disposition 1990; 11: 663-677
    CrossrefPubMedSearch in Google Scholar
  • 14 Edlund PO, Johansen K. Clean-up of plasma extracts by gel permeation chromatography during analysis of isosorbide nitrates by capillary gas chromatography. Journal of Chromatography A 1991; 553: 21-27
    CrossrefPubMedSearch in Google Scholar
  • 15 Gremeau I, Sautou V, Pinon V et al. Solid-phase extraction of isosorbide dinitrate and two of it metabolites from plasma for gas chromatographic analysis. Journal of Chromatography B: Biomedical Applications 1995; 665: 399-403
    CrossrefPubMedSearch in Google Scholar
  • 16 Pommier F, Gauducheau N, Pineau V et al. Simultaneous determination of isosorbide dinitrate and its mononitrate metabolites in human plasma by capillary gas chromatography with electron-capture detection. Journal of Chromatography B 1996; 678: 354-359
    CrossrefPubMedSearch in Google Scholar