Fadime CANBOLAT

Validation of Colchicine Assay Method for Therapeutic Drug Monitoring in Human Plasma

Colchicine (COL) reduces the frequency of attacks in Familial Mediterranean Fever (FMF) patients and is effective in preventing and arresting renal amyloidosis in most patients. COL has a narrow therapeutic window. The blood concentration to achieve therapeutic effects can be determined by Therapeutic Drug Monitoring (TDM). However, the use of selective and sensitive analytical methods is necessary for achieving success with TDM. The purpose of this study is to develop and validate a new method for quantitative assay of COL in human plasma samples by liquid chromatograph- tandem mass spectrometry (LC-MS/MS). In our study, to 1ml plasma sample, 0.25 ml internal standard solution was added. The solution was extracted by liquid-liquid extraction (LLE). The method was validated according to the European Medicines Agency (EMEA). The total run time was 8 min in LC-MS/MS. The method has been validated over the 0.25 - 8.0 ng/mL calibration range for COL. It was seen that the method has been validated since the results of the analysis meet the EMEA criteria. In our study, COL plasma levels were found to be approximately 1.097±0.42 ng/ml in 40 FMF patients using an oral dose of 1.5-2 mg/day. A validated, rapid, simple, cost-effective, and sensitive LC-MS/MS method was developed and optimized for quantitation of COL in plasma. It has been thought that pharmacokinetic studies of COL in plasma can be performed easily using this validated method

Keywords:

Colchicine, validation, plasma, Therapeutic Drug Monitoring LC-MS/MS,

PDF

___

Bourgogne, E., Soichot, M., Latour, C., & Laprévote, O. (2013). Rugged and accurate quantitation of colchicine in human plasma to support colchicine poisoning monitoring by using turbulent-flow LC–MS/MS analysis. Bioanalysis, 5(23), 2889-2896.
Canbolat, F., Ozen, G., Ozilhan, S., Gulturk, S., Ozcetin, A.,& Ozden, T. (2015a). Relationship Between Colchine Plasma Level and Frequency of Familial Mediterranean Fever Attacks. ACR/ARHP An-nual Meeting, Abstract 941, USA
Canbolat, F., Ozen, G., Ozilhan, S., Gulturk, S., Ozcetin, A., Unal, A. U., ... & Ozden, T. (2015b). THU0549 Relationship Between Colchine Plasma Level and Frequency of Familial Mediterranean Fever Attacks.BMJ Journals Annals of The Rheumatic Diseases, 74 (2).
Cerquaglia, C., Diaco, M., Nucera, G., Regina, M. L., Montalto, M., & Manna, R. (2005). Pharmacolo-gical and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update. Current Drug Targets-Inflammation & Allergy, 4(1), 117-124.
Cocco, G., Chu, D. C., & Pandolfi, S. (2010). Colchicine in clinical medicine. A guide for inter-nists. European journal of internal medicine, 21(6), 503-508.
Chèze, M., Deveaux, M., & Pèpin, G. (2006). Liquid chromatography-tandem mass spectrometry for the determination of colchicine in postmortem body fluids. Case report of two fatalities and re-view of the literature. Journal of analytical toxicology, 30(8), 593-598.
EMEA Committee for Medicinal Products for Human Use. Guideline on bioanalytical method valida-tion. European Medicines Agency EMEA. CHMP/EWP/192217/2009: 1-22 (cited 2011 August 01). Available from: www. ema. europa. eu/ema/pages/includes/document/open_document. jsp.
Fabresse, N., Allard, J., Sardaby, M., Thompson, A., Clutton, R. E., Eddleston, M., & Alvarez, J. C. (2017). LC–MS/MS quantification of free and Fab-bound colchicine in plasma, urine and organs following colchicine administration and colchicine-specific Fab fragments treatment in Göttingen minipigs. Journal of Chromatography B, 1060, 400-406.
Goldbart, A., Press, J., Sofer, S., & Kapelushnik, J. (2000). Near fatal acute colchicine intoxication in a child. A case report. European journal of pediatrics, 159(12), 895-897.
Gowda, B. G. (2014). High-Performance liquid chromatographic determination of colchicine in phar-maceutical formulations and biological fluids. Int. J Pharm Pharm Sci, 6, 335-337.
Jones, G. R., Singer, P. P., & Bannach, B. (2002). Application of LC-MS analysis to a colchicine fata-lity. Journal of analytical toxicology, 26(6), 365-369.
Lidar, M., Scherrmann, J. M., Shinar, Y., Chetrit, A., Niel, E., Gershoni-Baruch, R., ... & Livneh, A. (2004). Colchicine nonresponsiveness in familial Mediterranean fever: clinical, genetic, pharma-cokinetic, and socioeconomic characterization. In Seminars in arthritis and rheumatism (Vol. 33, No. 4, pp. 273-282). WB Saunders.
Niel, E., & Scherrmann, J. M. (2006). Colchicine today. Joint Bone Spine, 73(6), 672-678.
Tateishi, T., Soucek, P., Caraco, Y., Guengerich, F. P., & Wood, A. J. (1997). Colchicine biotransfor-mation by human liver microsomes: identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochemical pharmacology, 53(1), 111-116.
Tracqui, A., Kintz, P., Ludes, B., Rouge, C., Douibi, H., & Mangin, P. (1996). High-performance liquid chromatography coupled to ion spray mass spectrometry for the determination of colchicine at ppb levels in human biofluids. Journal of Chromatography B: Biomedical Sciences and Applica-tions, 675(2), 235-242.
Wason, S., DiGiacinto, J. L., & Davis, M. W. (2012). Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clinical therapeutics, 34(10), 2161-2173.