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Determination of Boc5 in Rat Plasma by HPLC–MS/MS and Its Application to a Pharmacokinetic Study

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Abstract

A simple, robust, and sensitive high-performance liquid chromatography tandem mass spectrometry method was developed and validated for determination of a new nonpeptidic glucose-like peptide-1 receptor (GLP-1R) agonist 1,3-bis(4-((p-butoxycarbonyl)amino)benzamido)-2,4-bis(m-methoxy-p-(thiophene-2-methanoyl)phenyl)-cyclobutane-1,3-dicarboxylic acid (Boc5) in rat plasma using wogonin as internal standard (IS). After a simple protein precipitation with methanol, chromatographic separation was achieved on an Atlantis T3 (100 mm × 4.6 mm, 3.5 μm) analytical column eluted by mobile phase consisting of methanol, acetonitrile, and 20 mM ammonium formate addition to 2% formic acid (39:39:22, v/v/v) at flow rate of 0.6 mL/min for 7 min. The quantitation analysis was performed using multiple reaction monitoring at the transitions of m/z 1,077.2 → 784.4 for Boc5 and m/z 285.1 → 270.4 for IS in positive ion mode with electrospray ionization source on an AB SCIEX API 4000 QTRAP mass spectrometer. Good linearity was achieved over the concentration range of 2–2,000 ng/mL with lower limit of quantification at 2 ng/mL. Intra- and interday precisions were less than 7.3 %, and accuracy ranged from −3.6 to 3.0 %. The mean recovery of Boc5 was 93.4–100.2 %, and the matrix effect of Boc5 was 88.0–93.8 %. The validated method was then successfully applied to a pharmacokinetic study of Boc5 in rats.

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References

  1. Kieffer TJ, Habener JF (1999) Endocr Rev 20:876

    Article  CAS  Google Scholar 

  2. Kim W, Egan JM (2008) Pharmacol Rev 60:470–512

    Article  CAS  Google Scholar 

  3. Neumiller JJ (2009) Am Pharm Assoc 49:16

    Article  Google Scholar 

  4. Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF, Gaeckler D, Schmidt WE, Gallwitz B (2004) Diabetes 53:654

    Article  CAS  Google Scholar 

  5. Van Genugten RE, Van Raalte DH, Diamant M (2009) Diabetes Res Clin Pract 86:26–34

    Article  Google Scholar 

  6. Croom KF, McCormack PL (2009) Drugs 69:1985

    Article  CAS  Google Scholar 

  7. Lotfy M, Singh J, Kalász H, Tekes K, Adeghate E (2011) Open Med Chem J 5:82–92

    Article  CAS  Google Scholar 

  8. Kieffer T, McIntosh CH, Pederson RA (1995) Endocrinology 136:85

    Article  Google Scholar 

  9. Chen DS, Liao JY, Li N, Zhou CH, Liu Q, Wang GX, Zhang R, Zhang S, Lin LL, Chen KX, Xie X, Nan FJ, Young AA, Wang MW (2007) Proc Natl Acad Sci USA 104:943

    Article  CAS  Google Scholar 

  10. Su HR, He M, Li HM, Liu Q, Wang J, Wang YQ, Gao WW, Zhou L, Liao JY, Young AA, Wang MW (2008) PLoS ONE 3:2892

    Article  Google Scholar 

  11. Wang MW, Liu Q, Zhou CH (2010) Acta Pharmacol Sin 1026:31

    Google Scholar 

  12. Murphy KG, Bloom SR (2007) Proc Natl Acad Sci USA 104:689

    Article  CAS  Google Scholar 

  13. FDA. Guidance for Industry, Bioanalytical Method Validation, FDA. http://www.fda.gov/cder/guidance

  14. Grobosch T, Schwarze B, Stoecklein D, Binscheck T (2012) J Anal Toxicol 36(1):36–43

    Article  CAS  Google Scholar 

  15. Uniyal GC, Bala S, Mathur AK, Kulkarni RN (2001) Phytochem Anal 12(3):206–210

    Article  CAS  Google Scholar 

  16. Koufopantelis P, Georgakakou S, Kazanis M, Giaginis C, Margeli A, Papargiri S, Panderi I (2009) J Chromatogr B 877(30):3850–3856

    Article  CAS  Google Scholar 

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Acknowledgments

This research was supported by Major State Basic Research Development Program of China (“973” Program) (no. 2010CB735602 and no. 2010CB933904).

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Authors and Affiliations

  1. Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Ruixing Li

  2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, China

    Ruixing Li, Huirong Fan, Yuan Gu & Duanyun Si

  3. Institute of Biophysics Chinese Academy of Sciences, Beijing, 100101, China

    Wei Liang

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  1. Ruixing Li
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  2. Huirong Fan
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  3. Yuan Gu
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  4. Duanyun Si
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  5. Wei Liang
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Correspondence to Duanyun Si.

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Li, R., Fan, H., Gu, Y. et al. Determination of Boc5 in Rat Plasma by HPLC–MS/MS and Its Application to a Pharmacokinetic Study. Chromatographia 75, 721–727 (2012). https://doi.org/10.1007/s10337-012-2248-y

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  • DOI: https://doi.org/10.1007/s10337-012-2248-y

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