Purification of homoharringtonine and removal of residual solvents by spray drying

Byung-Sik Kim; Jin-Hyun Kim

Korean Journal of Chemical Engineering, Vol.25, No.1, 108-111, January, 2008

DOI10.1007/s11814-008-0019-0 Export Citation

Purification of homoharringtonine and removal of residual solvents by spray drying

Byung-Sik Kim, and Jin-Hyun Kim^†

Department of Chemical Engineering, Kongju National University, 182, Shinkwan-dong, Kongju, Chungnam 314-701, Korea

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Homoharringtonine was purified from Cephalotaxus koreana by a combination of extraction, synthetic adsorbent treatment, low-pressure chromatography, and high performance liquid chromatography (HPLC). A crude extract was obtained by methanol extraction of biomass, followed by liquid-liquid extraction using chloroform. The waxy compounds were efficiently removed by adsorbent (active clay P-1) treatment. The extract was purified to greater than 52% with an 86.4% step yield by silica gel low-pressure chromatography. High performance liquid chromatography steps, which were composed of an HPLC step with silica column and an HPLC step with ODS column, were applied to give 98% purity with high yield. Amorphous homoharringtonine, with a fine particle size, was simply made by dissolving homoharringtonine in methylene chloride/methanol (98/2, v/v), followed by spray drying. Residual solvents, methylene chloride and methanol, could be reduced to 250 ppm and 1,160 ppm by spray drying and successive drying in a vacuum oven.

Keywords:Cephalotaxus koreana;Homoharringtonine (HHT);Purification;Residual Solvents;Spray Drying

[References]

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Castor TP, US Patent, 5,750,709 (1998)
Kim JH, Kang IS, Choi HK, Hong SS, Lee HS, Biotechnol. Lett., 22(22), 1753 (2000)
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ICH guidance Q3C impurities: Residual solvents, Federal register, 62(247), 67378 (1997)

[Referenced By]

[Related Articles]

[1] Grem JL, Cheson BD, King SA, Leyland-Jones B, Suffness M, J. Natl. Cancer Inst., 80, 1095 (1988)

[2] He J, Cheung AP, Wang E, Struble E, Fang K, Nguyen N, Liu P, J. Pharm. Biomed. Anal., 22, 541 (2000)

[3] Zhou DC, Zittoun R, Marie JP, Bull. Cancer., 82, 987 (1995)

[4] Luo CY, Tang JY, Wang YP, Hematology, 9, 259 (2004)

[5] Xie WZ, Lin MF, Huang H, Cai Z, Am. J. Chin. Med., 34, 233 (2006)

[6] Jin J, Jiang DZ, Mai WY, Meng HT, Qian WB, Tong HY, Huang J, Mao LP, Tong Y, Wang L, Chen ZM, Xu WL, Leukemia, 3, 1361 (2006)

[7] Beverly AB, Myron NC, Howard JW, Med. Pediatr. Oncol., 37, 103 (2000)

[8] Kantarjian HM, Talpaz M, Santini V, Murgo A, Cheson B, O’Brien SM, Cancer, 15, 1591 (2001)

[9] Efferth T, Davey M, Olbrich A, Rucker G, Gebhart E, Davey R, Blood Cells Mol. Dis., 28, 160 (2002)

[10] Wang DZ, Ma GE, Xu RS, Yaoxue Xuebao, 27, 178 (1992)

[11] Keller L, Dumas F, d’Angelo J, Tetrahedron Lett., 42, 1911 (2001)

[12] Liu Y, US Patent, 4,783,454 (1988)

[13] Castor TP, US Patent, 5,750,709 (1998)

[14] Kim JH, Kang IS, Choi HK, Hong SS, Lee HS, Biotechnol. Lett., 22(22), 1753 (2000)

[15] Gi US, Min B, Lee JH, Kim JH, Korean J. Chem. Eng., 21(4), 816 (2004)

[16] ICH guidance Q3C impurities: Residual solvents, Federal register, 62(247), 67378 (1997)