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盐酸美法仑光降解杂质的鉴定与含量测定

陈雪琴, 高芳, 廖明毅, 李瑞, 李薇, 丁黎

陈雪琴, 高芳, 廖明毅, 李瑞, 李薇, 丁黎. 盐酸美法仑光降解杂质的鉴定与含量测定[J]. 中国药科大学学报, 2017, 48(5): 590-595. DOI: 10.11665/j.issn.1000-5048.20170514
引用本文: 陈雪琴, 高芳, 廖明毅, 李瑞, 李薇, 丁黎. 盐酸美法仑光降解杂质的鉴定与含量测定[J]. 中国药科大学学报, 2017, 48(5): 590-595. DOI: 10.11665/j.issn.1000-5048.20170514
CHEN Xueqin, GAO Fang, LIAO Mingyi, LI Rui, LI Wei, DING Li. Identification and determination of the photodegradation impurities in melphalan hydrochloride[J]. Journal of China Pharmaceutical University, 2017, 48(5): 590-595. DOI: 10.11665/j.issn.1000-5048.20170514
Citation: CHEN Xueqin, GAO Fang, LIAO Mingyi, LI Rui, LI Wei, DING Li. Identification and determination of the photodegradation impurities in melphalan hydrochloride[J]. Journal of China Pharmaceutical University, 2017, 48(5): 590-595. DOI: 10.11665/j.issn.1000-5048.20170514

盐酸美法仑光降解杂质的鉴定与含量测定

Identification and determination of the photodegradation impurities in melphalan hydrochloride

  • 摘要: 对盐酸美法仑的光降解杂质PD1和PD2进行结构鉴定,并对PD1和PD2建立含量测定方法。通过LC-MS/MS法推测光降解杂质的结构,合成相应杂质,通过杂质比对确认光降解杂质。建立亲水作用色谱法对PD1和PD2进行含量测定,色谱柱为Atlantis HILIC柱(4.6 mm×150 mm,3 μm),流动相为0.1 mol/L甲酸铵溶液(甲酸调pH为3.0)-乙腈(13∶87),流速为1.0 mL/min,柱温为35 ℃,检测波长为260 nm。结果显示:光降解杂质PD1为4-氨基-L-苯丙氨酸盐酸盐,PD2为4-(2-氯乙基氨基)-L-苯丙氨酸盐酸盐;在建立的亲水作用色谱法中,盐酸美法仑与PD1、PD2可完全分离,建立的方法可用于光降解杂质的含量测定。
    Abstract: This study was aimed to identify the photodegradation impurities(PD1 and PD2)in melphalan hydrochloride and establish a method for determining PD1 and PD2. The structures of the photodegradation impurities were inferred by LC-MS/MS. The impurities were confirmed by comparing with synthesized impurities. An HILIC method was established to determine PD1 and PD2. The method was carried out on an Atlantis HILIC column(4. 6 mm×150 mm, 3 μm)with the mobile phase consisting of 0. 1 mol/L ammonium formate(adjusted to pH 3. 0 with formic acid)and acetonitrile(13∶87)at the flow rate of 1. 0 mL/min. The column temperature was 35 °C. The detection wavelength was 260 nm. PD1 and PD2 were characterized as 4-amino-L-phenylalanine hydrochloride and 4-(2-chloroethyl)amino-L-phenylalanine hydrochloride, respectively. Melphalan hydrochloride, PD1 and PD2 were separated completely under the HILIC condition. The established HILIC method can be used to determine the photodegradation impurities.
  • [1] Bogomilova A,Höhn M,Günther M,et al.A polyphosphoester conjugate of melphalan as antitumoral agent[J].Eur J Pharm Sci,2013,50(3):410-419.
    [2] Patel K,Parmar S,Shah S,et al.Comparison of subcutaneous versus intravenous alemtuzumab for graft-versus-host disease prophylaxis with fludarabine/melphalan-based conditioning in matched unrelated donor allogeneic stem cell transplantation[J].Biol Blood Marrow Transplant,2016,22(3):456-461.
    [3] Nooka AK,Harvey RD,Langston A,et al.Optimal dosing of melphalan as high-dose therapy before autologous hematopoietic stem cell transplantation in myeloma patients with solitary kidney:a case series[J].Clin Lymph Myelom Leuk,2014,14(2):59-63.
    [4] Bayraktar UD,Bashir Q,Qazilbash M,et al.Fifty years of melphalan use in hematopoietic stem cell transplantation[J].Biol Blood Marrow Transplant,2013,19(3):344-356.
    [5] Matsuo M,Yamaguchi K,Feril LB,et al.Synergistic inhibition of malignant melanoma proliferation by melphalan combined with ultrasound and microbubbles[J].Ultrason Sonochem,2011,18(5):1218-1224.
    [6] Munier FL,Gaillard MC,Balmer A,et al.Intravitreal chemotherapy for vitreous seeding in retinoblastoma:recent advances and perspectives[J].Saud J Ophthalmol,2013,27(3):147-150.
    [7] Scutaru AM,Wenzel M,Gust R.Bivalent bendamustine and melphalan derivatives as anticancer agents[J].Eur J Med Chem,2011,46(5):1604-1615.
    [8] Zhang N,Cui XY,Zhao XM,et al.Synthesis of melphalan derivatives and their antitumor activities[J].Drug Clin(现代药物与临床),2015,30(2):115-119.
    [9] Chinese Pharmacopoeia Commission.Chinese Pharmacopoeia:part 4(中华人民共和国药典:四部)[S].Beijing:China Medical Science Press,2015:354-356.
    [10] Wang YW,Li QS,Chen XS,et al.Photodissociation reaction of phosgene—first theoretical evidence for the asynchronously concerted three-body decay[J].Acta Chim Sin(化学学报),2003,61(9):1343-1345.
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出版历程
  • 刊出日期:  2017-10-24

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