Development and validation of a liquid chromatography tandem mass spectrometry assay for AZD3965 in mouse plasma and tumor tissue: Application to pharmacokinetic and breast tumor xenograft studies.
Development and validation of a liquid chromatography tandem mass spectrometry assay for AZD3965 in mouse plasma and tumor tissue: Application to pharmacokinetic and breast tumor xenograft studies.
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DOI：
10.1016/j.jpba.2018.03.061
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发表时间：
2018-06-05
影响因子：
3.4
通讯作者：
Morris ME
中科院分区：
文献类型：
--
作者：
Guan X;Ruszaj D;Morris ME
AZD3965是一种吡啶衍生物，是一种有效的口服生物可利用的单羧酸转运蛋白1 （MCT1）抑制剂，目前在英国进行用于淋巴瘤和实体瘤的I期临床试验。目前还没有发表的AZD3965检测方法。本研究的目的是建立并验证LC/MS/MS法定量小鼠血浆和肿瘤组织中的AZD3965。用0.1%甲酸在乙腈中沉淀蛋白质进行样品制备。在C18色谱柱上进行色谱分离，然后利用常压化学电离在多反应监测模式下进行串联质谱检测。内标采用AR-C155858。血浆和肿瘤组织中质量控制样品的日间和日间精密度和准确度均小于标称浓度的±7%。萃取回收率、基质效应和稳定性值均在可接受范围内。用空白血浆稀释AZD3965加标10倍的血浆获得的样品稀释完整性为101%。血浆中定量下限为0.15 ng/mL，定量上限为12 μg/ mL。该方法在肿瘤组织中也具有良好的精密度和准确性。肿瘤组织的限限为0.15 ng/mL。该方法成功地应用于AZD3965在小鼠体内的药代动力学和小鼠4T1乳腺肿瘤异种移植研究。
AZD3965, a pyrole pyrimidine derivative is a potent and orally bioavailable inhibitor of monocarboxylate transporter 1 (MCT1), currently in a Phase I clinical trial in UK for lymphomas and solid tumors. There is currently no published assay for AZD3965. The objectives of this study were to develop and validate a LC/MS/MS assay for quantifying AZD3965 in mouse plasma and tumor tissue. Protein precipitation with 0.1% formic acid in acetonitrile was used for sample preparation. Chromatographic separation was achieved on a C18 column followed by tandem mass spectrometry detection in multiple reaction monitoring mode with utilizing Atmospheric Pressure Chemical Ionization. AR-C155858 was used as the internal standard. The inter-day and intra-day precision and accuracy of quality control samples evaluated in plasma and tumor tissue were less than ±7% of the nominal concentrations. The extraction recovery, matrix effect and stability values were all within acceptable levels. Sample dilution integrity, accessed by diluting plasma spiked with AZD3965 10-fold with blank plasma, was 101%. The lower limit of quantification (LLOQ) and upper limit of quantification (ULOQ) were 0.15 ng/mL and 12 μg/ml, respectively, in plasma. The assay in tumor tissue was also validated with good precision and accuracy. The LLOQ was 0.15 ng/mL in tumor tissue. This assay was successfully applied to pharmacokinetic and murine 4T1 breast tumor xenograft studies of AZD3965 in mice.
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影响因子：
5.7
作者：
Bola BM;Chadwick AL;Michopoulos F;Blount KG;Telfer BA;Williams KJ;Smith PD;Critchlow SE;Stratford IJ
通讯作者：
Stratford IJ
影响因子：
--
作者：
Curtis NJ;Mooney L;Hopcroft L;Michopoulos F;Whalley N;Zhong H;Murray C;Logie A;Revill M;Byth KF;Benjamin AD;Firth MA;Green S;Smith PD;Critchlow SE
通讯作者：
Critchlow SE
影响因子：
11.2
作者：
Doherty JR;Yang C;Scott KE;Cameron MD;Fallahi M;Li W;Hall MA;Amelio AL;Mishra JK;Li F;Tortosa M;Genau HM;Rounbehler RJ;Lu Y;Dang CV;Kumar KG;Butler AA;Bannister TD;Hooper AT;Unsal-Kacmaz K;Roush WR;Cleveland JL
通讯作者：
Cleveland JL
影响因子：
15.9
作者：
Sonveaux, Pierre;Vegran, Frederique;Dewhirst, Mark W.
通讯作者：
Dewhirst, Mark W.
通过AZD3965抑制单羧酸酯转运蛋白转运蛋白1作为一种新型的弥漫性大型B细胞淋巴瘤和Burkitt淋巴瘤的治疗方法。
影响因子：
10.1
作者：
Noble RA;Bell N;Blair H;Sikka A;Thomas H;Phillips N;Nakjang S;Miwa S;Crossland R;Rand V;Televantou D;Long A;Keun HC;Bacon CM;Bomken S;Critchlow SE;Wedge SR
通讯作者：
Wedge SR