The analytical procedure for determination of Assay in finished product of Clofarabine Injection, 1mg/mL is an In-House procedure.

A new and stability-indicating High performance liquid chromatographymethod was developed and validated for simultaneous determination of clofarabine impurities in Injectionformulation.The Chromatographic system consisted of a Shimadzu Class VP Binary pump LC-10ATvp, SIL-10ADvp Auto sampler, CTO-10Avp Column Temperature Oven, SPD-10Avp UV-Visible Detector.The method was validated as per the ICH guidelines Apart from these Chromatographic parameters likeresolution, capacity factor, separation factor, column efficiency and peakasymmetry should also be the ideal for estimation.

Clinical efficacy of combined or single use of clofibrate and cytarabine in treatment of adult patients with myelodysplastic syndromes or acute leukemia: a Meta analysis / 白血病·淋巴瘤

Objective To analyze the clinical efficacy of combined or single use of clofibrate and cytarabine in the treatment of adult patients with myelodysplastic syndromes (MDS) or acute leukemia (AL).Methods Clofarabine combined with cytarabine was used in the combined group and clofarabine or cyarabine alone was used in the control group.All the studies about cytarabine and clofarabine were searched in PubMed,Cochrance Library,Embase,CNKI,Wanfang and VIP database by computer,and then the data was extracted.Results The complete remission rate of the combined group was higher than that of the control group [33.1％ (93/281) vs.18.2％ (35/192),and the difference was statistically significant (RR =1.85,95％ CI 1.31-2.60,P ＜ 0.01).The overall response rate of the combined group was higher than that of the control group [44.0％ (124/282) vs.23.2％ (46/198)],and the difference was statistically significant (RR =1.92,95％ CI 1.44-2.56,P ＜ 0.01).However,the incidence of skin adverse reactions in the combined group was also higher than that in the control group [38.8％ (104/268) vs.3.1％ (6/192)],and the difference was statistically significant (RR =7.76,95％ CI 3.68-16.38,P ＜ 0.01).Conclusion The combination of clofarabine and cytarabine in the treatment of adult patients with MDS or AL has better clinical efficacy than single application,but it also has more serious skin adverse reactions.

Clofarabine: a next-generation deoxyadenosine analogue

Acute lymphoblastic leukaemia (ALL) is the most common of the paediatric leukaemias. It is estimated that the use of modern combination chemotherapy results in long-term remission in nearly 80% of children diagnosed with ALL. Despite therapy advances, approximately 20% of children with ALL, experience leukaemia relapse. Clofarabine (2-chloro-2’-fluoro-2’-deoxy-9-?-D-arabinofuranosyladenine) is a second-generation nucleoside analogue and is structurally related to fludarabine and cladribine which are widely used in the treatment of lymphoproliferative disorders. Clofarabine exhibits greater affinity to deoxycytidine kinase (dCyd kinase) and prolonged retention in leukaemic blasts compared to fludarabine and cladribine. Clofarabine inhibits both DNA polymerases and ribonucleotide reductase (RNR). This results in impaired DNA synthesis through inhibition of DNA elongation as well as depletion of deoxyribonucleotides. Accumulation of clofarabine triphosphate, in the blasts of patients with refractory leukemia has been demonstrated. Prolonged intracellular half-life of 24 hours for clofarabine triphosphate. Clofarabine is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.

Knockdown of Bcl-xL Enhances Growth-Inhibiting and Apoptosis-Inducing Effects of Resveratrol and Clofarabine in Malignant Mesothelioma H-2452 Cells

Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.

Determination of Residual Organic Solvents in Clofarabine by GC / 中国药房

OBJECTIVE:To establish a gas chromatography(GC)method for determination of seven residual solvents in clofarabine.METHODS:The capillary column was AT-1301;the carrier gas was nitrogen gas and the detector was FID.By temperature programming was applied for the column temperature with an initial temperature of 40 ℃,which rose to 80 ℃ with an increase rate of 7 ℃?min-1,then rose to 200 ℃(kept at this temperature for 2 min)with the increase rate of 20 ℃?min-1.The injector temperature was 250 ℃ and the detector temperature was 280 ℃.The sample was injected directly for determination of residual levels of methanol,acetonitrile,dichlormethane,t-butyl alcohol,ethyl acetate,n-heptane and acetic acid in 3 batches of clofarabine.RESULTS:All the organic solvents were effectively separated and they showed good linearity within a concentration range(r=0.999 41～0.999 93)with average recovery rate ranged from 96.5% to 102.4%(RSDs of all were less than 4.0%).7 kinds of organic solvents in 3 batches of samples were all up to the standard specified in Chinese Pharmacopeia.CONCLUSION:The method is sensitive,accurate and reliable,and it is applicable for the determination of the residual solvents in clofarabine.