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Arzneimittelforschung 2011; 61(3): 141-147
DOI: 10.1055/s-0031-1296180
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Determination of glyceryl trinitrate and its two main metabolites in human plasma using a new sensitive gas chromatography method

Mohammadreza Ghandforoush-Sattari
1   Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
2   Haematology and Oncology Research Center, Tabriz University of Medical Science, Tabriz, Iran
3   Infectious and Tropical Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran
,
Parvin Zakeri-Milani
4   Drug Applied Research Center, Tabriz University of Medical Science, Tabriz, Iran
1   Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
,
Siminozar Mashayekhi
1   Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
5   National Public Health Management Centre (NPMC), Tabriz University of Medical Science, Tabriz, Iran
,
Hadi Valizadeh
6   Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Science, Tabriz, Iran
1   Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
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Publikationsverlauf

Publikationsdatum:
28. November 2011 (online)

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Abstract

The aim of the present study was to determine the concentrations of nitroglycerin (glyceryl trinitrate, GTN, CAS 55-63-0) and its two main stable metabolites; 1,2-dinitroglycerin (1,2-glyceryl dinitrate, GDN, CAS 621-65-8) and 1,3-dinitrogly-cerin (1,3-GDN, CAS 623-87-0) in human plasma using a capillary gas chromatography method with an electron capture detection. Using the GC conditions, linear calibrations were obtained for 1,3-GDN from 0.14 to 3 ng/mL, for 1,2-GDN from 0.06 to 6 ng/mL, and for GTN from 0.01 to 0.3 ng/mL in plasma samples by the following calibration curve equations: [y = 0.1924x − 0.0088 (r2 = 0.999)], [y = 0.2273x + 0.0164 (r2 = 0.995)], [y = 17.434x − 0.0751] for 1,3-GDN, 1,2-GDN, and GTN respectively. The calculated limits of quantification values for GTN, 1,2-GDN, and 1,3-GDN were 0.03 ng/mL, 0.2 ng/mL, and 0.15 ng/mL respectively. This method was verified with a bioequivalence study of an Iranian brand of oral sustained release nitroglycerin with an innovator formulation.

Key words

CAS 55-63-0 - Gas chromatography - Glyceryl trinitrate - Bioequivalence - Nitroglycerin - Pharmacokinetics
 

  • References

  • 1 Hutt V, Sauter K, Pabst G, Bonn R, Fritschi E. Bioequivalence evaluation of the metabolites 1,2 and 1,3-glyceryl di-nitrate of two different glyceryl trinitrate patches after 12-h usage in healthy volunteers. Arzneimittelforschung. 1994; 44 (12) 1317-21
    PubMedGoogle Scholar
  • 2 Abshagen U, Betzien G, Endele R, Kaufmann B, Neugebauer G. Pharmacokinetics and metabolism of isosorbide-dinitrate after intravenous and oral administration. Eur J Clin Pharmacol. 1985; 27 (6) 637-44
    CrossrefPubMedGoogle Scholar
  • 3 Kwon HR, Green P, Curry SH. Pharmacokinetics of nitroglycerin and its metabolites after administration of sustained-release tablets. Biopharm Drug Dispos. 1992; 13 (2) 141-52
    CrossrefPubMedGoogle Scholar
  • 4 Leitold M, Laufen H, Yeates RA. [Comparative pharmacology of glycerol-1-nitrate and glyceryl trinitrate in various species]. Arzneimittelforschung. 1986; 36 (5) 814-21
    PubMedGoogle Scholar
  • 5 Armstrong JA, Slaughter SE, Marks GS, Armstrong PW. Rapid disappearance of nitroglycerin following incubation with human blood. Can J Physiol Pharmacol. 1980; 58 (5) 459-62
    CrossrefPubMedGoogle Scholar
  • 6 Nakashima E, Rigod JF, Lin ET, Benet LZ. Pharmacokinetics of nitroglycerin and its dinitrate metabolites over a thirtyfold range of oral doses. Clin Pharmacol Ther. 1990; 47 (5) 592-8
    CrossrefPubMedGoogle Scholar
  • 7 Miyayama T, Tsou PS, Fung SM, Fung HL. Simultaneous determination of nitroglycerin and dinitrate metabolites in metabolism studies using liquid chromatography-mass spectrometry with electrospray ionization. J Chromatogr B Analyt Technol Biomed Life Sci. 2006; 835 (1–2) 21-6
    PubMedGoogle Scholar
  • 8 Blumenthal HP, Fung HL, McNiff EF, Yap SK. Plasma nitroglycerin levels after sublingual, oral and topical administration. Br J Clin Pharmacol. 1977; 4 (2) 241-2
    CrossrefPubMedGoogle Scholar
  • 9 Gerardin A, Gaudry D, Wantiez D.. Gas chromatographic mass spectrometric determination of 1,2,3-propanetriol-trinitrate (nitroglycerin) in human plasma using the nitrogen-15 labelled compound as internal standard. Biomed Mass Spectrom. 1982; 9 (8) 333-5
    CrossrefPubMedGoogle Scholar
  • 10 Idzu G, Ishibashi M, Miyazaki H, Yamamoto K. Determination of glyceryl trinitrate in human plasma by gas chroma-tography-negative ion chemical ionization-selected ion monitoring. J Chromatogr. 1982; 229 (2) 327-36
    CrossrefPubMedGoogle Scholar
  • 11 Ottoila P, Taskinen J, Sothmann A. Quantitative determination of nitroglycerin in human plasma by capillary gas chromatography negative ion chemical ionization mass spectrometry. Biomed Mass Spectrom. 1982; 9 (3) 108-10
    CrossrefPubMedGoogle Scholar
  • 12 Baba S, Shinohara Y, Sano H, Inoue T, Masuda S, Kurono M. Application of high-performance liquid chromatography with synchronized accumulating radioisotope detector to analysis of glyceryl trinitrate and its metabolites in rat plasma. J Chromatogr. 1984; 305 (1) 119-26
    CrossrefPubMedGoogle Scholar
  • 13 Spanggord RJ, Keck RG. Application of high-pressure liquid chromatography and thermal energy analyzer to analysis of trinitroglycerin and its metabolites in blood. J Pharm Sci. 1980; 69 (4) 444-6
    CrossrefPubMedGoogle Scholar
  • 14 Rosseel MT, Bogaert MG. GLC determination of nitroglycerin and isosorbide dinitrate in human plasma. J Pharm Sci. 1973; 62 (5) 754-758
    CrossrefPubMedGoogle Scholar
  • 15 Viswanathan CT, Bansal S, Booth B, DeStefano AJ, Rose MJ, Sailstad J et al. Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays. Pharm Res. 2007; 24 (10) 1962-73
    CrossrefPubMedGoogle Scholar
  • 16 Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray If et al. Bioanalytical method validation-a revisit with a decade of progress. Pharm Res. 2000; 17 (12) 1551-7
    CrossrefPubMedGoogle Scholar
  • 17 Shah VP, Midha KK, Dighe S, McGilveray IJ, Skelly JP, Yacobi A et al. Analytical methods validation: bioavailability, bioequivalence and pharmacokinetic studies. Conference report. Eur J Drug Metab Pharmacokinet. 1991; 16 (4) 249-55
    CrossrefPubMedGoogle Scholar
  • 18 Karnes HT, Shiu G, Shah VP. Validation of bioanalytical methods. Pharm Res. 1991; 8 (4) 421-6
    CrossrefPubMedGoogle Scholar
  • 19 Zakeri-Milani P, Valizadeh H, Ghanbarzadeh S, Nemati M. Pharmacokinetics and comparative bioavailability study of two clarithromycin suspensions following administration of a single oral dose to healthy volunteers. Arzneimittelforschung. 2009; 59 (8) 429-32
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 20 Valizadeh H, Barghi L, Jalilian H, Islambulchilar Z, Zakeri-Milani P. Bioequivalence of fexofenadine tablet formulations assessed in healthy Iranian volunteers. Arzneimittelforschung. 2009; 59 (7) 345-9
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 21 Zakeri-Milani P, Valizadeh H, Islambulchilar Z. Comparative bioavailability study of two Cefixime formulations administered orally in healthy male volunteers. Arzneimittelforschung. 2008; 58 (2) 97-100
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 22 FDA [Internet]. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); 2003 [cited 2010 Jul 26]. Guidance for industry, bioavailability and bioequivalence studies for orally administered drug products; General considerations. Available from: http://www.fda.gov/cder/guidancel5356fnl.pdf
    PubMed
  • 23 EMA [Internet]. London (UK): European Medicines Agency Committee for Medicinal Products for Human Use (CHMP); 2008 [cited 2010 Jul 26]. Guideline on the Investigation of Bioequivalence. Pre-Authorisation Evaluation of Medicines for Human Use. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientiflc_guideline/2009/09/WC500003011.pdf
    PubMed
  • 24 Zakeri-Milani P, Valizadeh H. Comparative bioavailability study of two olanzapine formulations administered orally in healthy male volunteers. Pharmacy World Sci. 2008; 30 (5) 702-3
    PubMedGoogle Scholar
  • 25 Zakeri-Milani P, Valizadeh H, Islambulchilar Z, Nemati M. Pharmacokinetic and bioequivalence study of two brands of valsartantabletsinhealthymale volunteers. Arzneimittelforschung. 2010; 60 (2) 76-80
    PubMedGoogle Scholar
  • 26 Lee FW, Watari N, Rigod J, Benet LZ. Simultaneous determination of nitroglycerin and its dinitrate metabolites by capillary gas chromatography with electron-capture detection. J Chromatogr. 1988; 426 (2) 259-66
    CrossrefPubMedGoogle Scholar
  • 27 Valizadeh H, Zakeri-Milani P, Islambulchilar Z, Tajerzadeh H. A simple and rapid high-performance liquid chromatography method for determining furosemide, hydrochlorothiazide, and phenol red: applicability to intestinal permeability studies. J AOAC Int. 2006; 89 (1) 88-93
    PubMedGoogle Scholar
  • 28 Zakeri-Milani P, Barzegar-Jalali M, Tajerzadeh H, Azarmi Y, Valizadeh H. Simultaneous determination of naproxen, ketoprofen and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation. J Pharm Biomed Anal. 2005; 39 (3–4) 624-30
    CrossrefPubMedGoogle Scholar
  • 29 Islambulchilar Z, Valizadeh H, Zakeri-Milani P. Rapid HPLC determination of pioglitazone in human plasma by protein precipitation and its application to pharmacokinetic studies. J AOAC Int. 2010; 93 (3) 876-81
    PubMedGoogle Scholar
  • 30 Ghandforoush-Sattari MR, Mashayekhi SO, Nemati M, Routledge PA. A rapid determination of taurine in human plasma by LC. Chromatoghraphia. 2009; 69 (11–12) 1-4
    PubMedGoogle Scholar
  • 31 Ghandforoush-Sattari MR, Valizadeh H, Zakeri-Milani P, Mashayekhi SO. Comparative bioavailability of two brands of oral sustained-release nitroglycerin tablets. In: Ghandforoush-Sattari MR. editor. The 68th FIP World Congress of Pharmacy and Pharmaceutical Sciences. Basel, Switzerland: FIP; 2008
    Google Scholar
  • 32 Marks GS, McLaughlin BE, MacMillan HF, Nakatsu K, Brien JF. Differential biotransformation of glyceryl trinitrate by red blood cell-supernatant fraction and pulmonary vein homogenate. Can J Physiol Pharmacol. 1989; 67 (5) 417-22
    CrossrefPubMedGoogle Scholar
  • 33 Han C, Jung P, Sanders SW, Lin ET, Benet LZ. Pharmacokinetics of nitroglycerin and its four metabolites during nitroglycerin transdermal administration. Biopharm Drug Dispos. 1994; 15 (2) 179-83
    CrossrefPubMedGoogle Scholar
  • 34 Yu DK, Williams RL, Benet LZ, Lin ET, Giesing DH. Pharmacokinetics of nitroglycerin and metabolites in humans following oral dosing. Biopharm Drug Dispos. 1988; 9 (6) 557-65
    CrossrefPubMedGoogle Scholar
  • 35 Noonan PK, Kanfer I, Riegelman S, Benet LZ. Determination of picogram nitroglycerin plasma concentrations using capillary gas chromatography with on-column injection. J Pharm Sci. 1984; 73 (7) 923-7
    CrossrefPubMedGoogle Scholar
  • 36 Scharpf F, Yeates RA, Laufen H, Eibel G. Gas chromatographic assay of glycerol mononitrates in biological samples. J Chromatogr. 1987; 413: 91-9
    CrossrefPubMedGoogle Scholar