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.
References
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
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
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
Koul A, Arnoult E, Lounis N, Guillemont J, Andries K (2011) The challenge of new drug discovery for tuberculosis. Nature 469(7331):483–490
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
Xu HB, Jiang RH, Xiao HP (2012) Clofazimine in the treatment of multidrug-resistant tuberculosis. Clin Microbiol Infect 18(11):1104–1110
Cholo MC, Steel HC, Fourie PB, Germishuizen WA, Anderson R (2012) Clofazimine: current status and future prospects. J Antimicrob Chemother 67(2):290–298
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
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
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
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
O’connor R, O’sullivan J, O’kennedy R (1995) The pharmacology, metabolism, and chemistry of clofazimine. Drug Metab Rev 27(4):591–614
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
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
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
Corresponding author
Rights and permissions
About this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10337-014-2771-0