Skip to main content
Log in

Determination of TBI-166, a Novel Antituberculotic, in Rat Plasma by Liquid Chromatography–Tandem Mass Spectrometry

  • Short Communication
  • Published:
Chromatographia Aims and scope Submit manuscript

Abstract

A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of TBI-166 in rat plasma was developed and validated. Propranolol was used as the internal standard (IS). Plasma samples containing TBI-166 and IS were prepared based on a simple protein precipitation by the addition of ten volumes of acetonitrile. Thermo Scientific TSQ Quantum triple quadrupole system with multiple reaction monitoring (MRM) positive scanning mode was applied. The monitored transitions were 590 → 478 for TBI-166 and 260 → 183 for IS. The separation was performed on a Symmetry C8 column (3.5 μm, 2.1 × 50 mm) with the mobile phase of acetonitrile/water containing 0.1 % formic acid (v/v) with gradient elution at a flow rate of 0.2 mL/min. Linear detection responses were obtained for TBI-166 ranging from 5 to 2000 ng/mL and the lower limit of quantitation (LLOQ) was 5 ng/mL. The intra- and inter-day precisions (RSD) were all within 7.2 %, while the deviation of assay accuracies was equal to or lower than ±5.5 %. The average recoveries of analyte were greater than 95.2 %. The analyte was proved to be stable during all sample storage, preparation and analytic procedures. The optimized method was successfully applied to the pharmacokinetic studies of TBI-166 in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Hanefeld J (2014) The Global Fund to Fight AIDS, Tuberculosis and Malaria: 10 years on. Clin Med 14(1):54–57. doi:10.7861/clinmedicine.14-1-54

    Article  Google Scholar 

  2. Adams KN, Szumowski JD, Ramakrishnan L (2014) Verapamil, and its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs. J Infect Dis. doi:10.1093/infdis/jiu095

    Google Scholar 

  3. Palmer BD, Thompson AM, Sutherland HS, Blaser A, Kmentova I, Franzblau SG, Wan B, Wang Y, Ma Z, Denny WA (2009) Synthesis and structure–activity studies of biphenyl analogues of the tuberculosis drug (6 S)-2-Nitro-6-{[4-(trifluoromethoxy) benzyl] oxy}-6, 7-dihydro-5 H-imidazo [2, 1-b][1, 3] oxazine (PA-824). J Med Chem 53(1):282–294

    Article  Google Scholar 

  4. Koul A, Arnoult E, Lounis N, Guillemont J, Andries K (2011) The challenge of new drug discovery for tuberculosis. Nature 469(7331):483–490

    Article  CAS  Google Scholar 

  5. Barry VC, Belton J, Conalty ML, Denneny JM, Edward DW, O’sullivan J, Twomey D, Winder F (1957) A new series of phenazines (rimino-compounds) with high antituberculosis activity. Nature 179:1013–1015

    Article  CAS  Google Scholar 

  6. Xu HB, Jiang RH, Xiao HP (2012) Clofazimine in the treatment of multidrug-resistant tuberculosis. Clin Microbiol Infect 18(11):1104–1110

    Article  CAS  Google Scholar 

  7. Cholo MC, Steel HC, Fourie PB, Germishuizen WA, Anderson R (2012) Clofazimine: current status and future prospects. J Antimicrob Chemother 67(2):290–298

    Article  CAS  Google Scholar 

  8. Kasim NA, Whitehouse M, Ramachandran C, Bermejo M, Lennernäs H, Hussain AS, Junginger HE, Stavchansky SA, Midha KK, Shah VP (2004) Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol Pharm 1(1):85–96

    Article  CAS  Google Scholar 

  9. Lu Y, Zheng M, Wang B, Fu L, Zhao W, Li P, Xu J, Zhu H, Jin H, Yin D (2011) Clofazimine analogs with efficacy against experimental tuberculosis and reduced potential for accumulation. Antimicrob Agent Chemother 55(11):5185–5193

    Article  CAS  Google Scholar 

  10. Sandler E, Ng V, Hadley W (1992) Clofazimine crystals in alveolar macrophages from a patient with the acquired immunodeficiency syndrome. Arch Pathol Lab Med 116(5):541–543

    CAS  Google Scholar 

  11. Job CK, Yoder L, Jacobson RR, Hastings RC (1990) Skin pigmentation from clofazimine therapy in leprosy patients: a reappraisal. J Am Acad Dermatol 23(2):236–241

    Article  CAS  Google Scholar 

  12. O’connor R, O’sullivan J, O’kennedy R (1995) The pharmacology, metabolism, and chemistry of clofazimine. Drug Metab Rev 27(4):591–614

    Article  Google Scholar 

  13. Baik J, Stringer KA, Mane G, Rosania GR (2013) Multiscale distribution and bioaccumulation analysis of clofazimine reveals a massive immune system-mediated xenobiotic sequestration response. Antimicrob Agents Chemother 57(3):1218–1230. doi:10.1128/aac.01731-12

    Article  CAS  Google Scholar 

  14. Zhang D, Lu Y, Liu K, Liu B, Wang J, Zhang G, Zhang H, Liu Y, Wang B, Zheng M, Fu L, Hou Y, Gong N, Lv Y, Li C, Cooper CB, Upton AM, Yin D, Ma Z, Huang H (2012) Identification of less lipophilic riminophenazine derivatives for the treatment of drug-resistant tuberculosis. J Med Chem 55(19):8409–8417. doi:10.1021/jm300828h

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Global Alliance for TB Drug Development, the National Science and Technology Major Project of China (2012ZX09301002-001-007, 2011ZX09102-001-01, 2012ZX09301002-006, 2012ZX09103-101-001). The authors would like to acknowledge Ms. Hu, Ms. Chen and Mr. Wang for their technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yan Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, D., Sheng, L., Liu, X. et al. Determination of TBI-166, a Novel Antituberculotic, in Rat Plasma by Liquid Chromatography–Tandem Mass Spectrometry. Chromatographia 77, 1697–1703 (2014). https://doi.org/10.1007/s10337-014-2771-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10337-014-2771-0

Keywords

Navigation