Simultaneous Determination of Diastereomers (+)-Licarin A and Isolicarin A from Myristica fragrans in Rat Plasma by HPLC and its Application to their Pharmacokinetics

Abstract

A rapid and simple high-performance liquid chromatographic (HPLC) method was developed and validated to simultaneously analyze the diastereomers of (+)-licarin A and isolicarin A in rat plasma after intravenous administration. The analytes were extracted from the plasma by solid-phase extraction (SPE). Diastereomeric separation and determination were successfully achieved using a Diamonsil™ ODS C₁₈ reversed-phase column (250 mm × 4.6 mm i. d., 5 μm) with an RP18 guard column (8 mm × 4.6 mm i. d., 5 μm) and a mobile phase of MeOH-H₂O (4 : 1, v/v). UV detection was at 270 nm. The linear ranges of the standard curves were 0.25 – 150.00 μg/mL for (+)-licarin A and 0.10 – 75.00 μg/mL for isolicarin A. The lower limits of detection and quantification were 0.05 and 0.25 μg/mL for (+)-licarin A, and 0.05 and 0.10 μg/mL for isolicarin A, respectively. This assay method was successfully applied to study the pharmacokinetics of diastereomers (+)-licarin A and isolicarin A in rat plasma.

Abbreviations

HPLC:high-performance liquid chromatography

LLOD:lower limits of detection

LLOQ:lower limits of quantification

QC:quality control

R.S.D.:relative standards deviation

SD:Sprague-Dawley

SPE:solid-phase extraction

UV:ultraviolet

Key words

Myristica fragrans - Myristicaceae - (+)-licarin A - isolicarin A - diastereomers - pharmacokinetics - HPLC

References

• 1 The State Pharmacopoeia Commission of P. R. China. Chin Pharmacopoeia, Vol. 1. Beijing; Chemical Industry Press 2005: 102-3
• 2 Van G C, Cox P A. Ethnobotany of nutmeg in the spice islands.  J Ethnopharmacol. 1994;  42 117-24
• 3 Yang X W, Huang X, Aihemat M. New neolignan from seed of Myristica fragrans. .  China J Chin Mater Med. 2008;  33 397-402
• 4 Hattori M, Hada S, Watahiki A, Ihara H, Shu Y Z, Kakiuchi N. et al . Studies on dental caries prevention by traditional medicines: Antibacterial action of phenolic components from mace against Streptococcus mutans. .  Chem Pharm Bull. 1986;  34 3885-93
• 5 Murakami Y, Shoji M, Hirata A, Tanaka S, Yokoe I, Fujisawa S. Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide- stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages.  Arch Biochem Biophys. 2005;  434 326-32
• 6 Hattori M, Yang X W, Miyashiro H, Namba T. Inhibitory effects of monomeric and dimeric phenylpropanoids from mace on lipid peroxidation in vivo and in vitro. .  Phytother Res. 1993;  7 395-401
• 7 Shin K H, Woo W S. Inhibition and induction of hepatic mixed function oxidase by phenylpropanoids from the seeds of Myristica fragrans. .  Han′guk Saenghwa Hakhoechi. 1990;  23 122-7
• 8 Food and Drug A dministration. FDA′S policy statement for the development of new stereoisomeric drugs.  Chirality. 1992;  4 338-40
• 9 Mil’anová C, Hutta M. Role of biological matrices during the analysis of chiral drugs by liquid chromatography.  J Chromatogr B. 2003;  797 91-109
• 10 Caldwell J. Stereochemical determinants of the nature and consequences of drug metabolism.  J Chromatogr A. 1995;  694 39-48
• 11 Yan K, Song H, Lo M. Determination of MK-0767 enantiomers in human plasma by normal phase LC–MS/MS.  J Chromatogr B. 2004;  813 95-102
• 12 Lipka E, Selouane A, Postel D, Len C, Vaccher M P, Bonte J P. et al . Enantioseparation of four cis and trans diastereomers of 2′,3′-didehydro-2′,3′-dideoxythymidine analogs, by high-performance liquid chromatography and capillary electrophoresis.  J Chromatogr A. 2004;  1034 161-7
• 13 Naidong W, Pullen R H, Arrendale R F, Brennan J J, Hulse J D, Lee J W. Stereospecific determinations of (±)-DU-124 884 and its metabolites (±)-KC-9048 in human plasma by liquid chromatography.  J Pharm Biomed Anal. 1996;  14 325-7
• 14 Park T H, Kim J K, Jee J P, Park J S, Kim C K. HPLC method for simultaneous determination of cefprozil diastereomers in human plasma.  J Pharm Biomed Anal. 2004;  36 243-8
• 15 Miura M, Uno T, Tateishi T, Suzuki T. Determination of fexofenadine enantiomers in human plasma with high-performance liquid chromatography.  J Pharm Biomed Anal. 2007;  43 741-5
• 16 Hefnawy M M, Aboul-Enein H Y. A validated LC method for the determination of vesamicol enantiomers in human plasma using vancomycin chiral stationary phase and solid phase extraction.  J Pharm Biomed Anal. 2004;  35 535-43
• 17 Gui F J, Yang X W. Simultaneous enantiomer determination of 20 (R)- and 20 (S)-ginsenoside-Rg₂ in rat plasma after intravenous administration using HPLC method.  J Chromatogr B. 2007;  850 1-6
• 18 Franco V, Mazzucchelli I, Fattore C, Marchiselli R, Gatti G, Perucca E. Stereoselective determination of vigabatrin enantiomers in human plasma by high performance liquid chromatography using UV detection.  J Chromatogr B. 2007;  854 63-7
• 19 Zhang Y, Akao N, Nakamura N, Duan C L, Hattori M, Yang X W. et al . Extremely low bioavailability of magnesium lithospermate B, an active component from Salvia miltiorrhiza, in rat.  Planta Med. 2004;  70 138-42
• 20 Malm M, Bergqvist Y. Determination of eflornithine enantiomers in plasma, by solid-phase extraction and liquid chromatographywith evaporative light-scattering detection.  J Chromatogr B. 2007;  846 98-104
• 21 Hou J G, Zheng J, Shamsi S A. Separation and determination of warfarin enantiomers in human plasmausing a novel polymeric surfactant for micellar electrokinetic chromatography-mass spectrometry.  J Chromatogr A. 2007;  1159 208-16
• 22 Sabarinath S, Singh R P, Gupta R C. Simultaneous quantification of α-/β-diastereomers of arteether, sulphadoxineand pyrimethamine: A promising anti-relapse antimalarial therapeuticcombination, by liquid chromatography tandem mass spectrometry.  J Chromatogr B. 2006;  842 36-42
• 23 Reineke A K, Preiss A, Elend M, Hollender J. Detection of methylquinoline transformation products in microcosm experiments and in tar oil contaminated groundwater using LC-NMR.  Chemosphere. 2008;  70 2118-26
• 24 Hassan Y, Aboul-Enein Vince S. Direct enantioselective separation of bevantolol by high performance liquid chromatography on normal and reverse cellulose chiral stationary phases.  Biomed Chromatogr. 1994;  8 22-5
• 25 Kim K H, Kim H J, Kang J S, Mar W. Determination of metoprolol enantiomers in human urine by coupled achiral-chiral chromatography.  J Pharm Biomed Anal. 2000;  22 377-84
• 26 Inoue Y, Shinka T, Ohse M, Ikawa H, Kuhara T. Application of optical isomer analysis by diastereomer derivatization GC/MS to determine the condition of patients with short bowel syndrome.  J Chromatogr B. 2006;  838 37-42
• 27 Li F, Yang X W. Three new neolignans from the aril of Myristica fragrans.  Helv Chim Acta. 2007;  90 1491-6