Kim Jihye, Abdulwahab Sara, Choi Kihwan, Lafrenière Nelson M, Mudrik Jared M, Gomaa Hala, Ahmado Hend, Behan Lucy-Ann, Casper Robert F, Wheeler Aaron R
†Department of Chemistry, University of Toronto, 80 Saint George Street, Toronto, Ontario M5S 3H6, Canada.
§Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Anal Chem. 2015;87(9):4688-95. doi: 10.1021/ac5043297. Epub 2015 Apr 20.
Core needle biopsy (CNB) sampling is known to be inexpensive and minimally invasive relative to traditional tissue resectioning. But CNBs are often not used in analytical settings because of the tiny amount of sample and analyte. To address this challenge, we introduce an analytical method capable of multiplexed steroid quantification in CNB samples-those studied here ranged in mass from 2 to 8 mg. The new method uses digital microfluidics to extract steroids from CNB tissue samples (including a solid-phase extraction cleanup step) followed by analysis by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The method has limits of detection of 3.6, 1.6, 5.8, and 8.5 fmol for estradiol, androstendione, testoterone, and progesterone, respectively. We propose that future generations of this method may be useful for regular quantification of steroids in core needle biopsy samples of breast tissue to inform dosage and timing of antihormone or hormone replacement therapies as part of a personalized medicine approach to treating a variety of hormone-sensitive disorders.
相对于传统的组织切除,粗针活检(CNB)采样已知成本低廉且微创。但由于样本和分析物量极少,CNB在分析环境中往往不被采用。为应对这一挑战,我们引入了一种能够对CNB样本中的类固醇进行多重定量分析的方法——此处研究的样本质量在2至8毫克之间。新方法利用数字微流控技术从CNB组织样本中提取类固醇(包括固相萃取净化步骤),随后通过高效液相色谱串联质谱(HPLC-MS/MS)进行分析。该方法对雌二醇、雄烯二酮、睾酮和孕酮的检测限分别为3.6、1.6、5.8和8.5飞摩尔。我们认为,该方法的后续版本可能有助于定期定量乳腺组织粗针活检样本中的类固醇,从而为抗激素或激素替代疗法的剂量和时机提供依据,作为治疗各种激素敏感性疾病的个性化医疗方法的一部分。