A method to directly analyze free-drug–related species in antibody-drug conjugates without sample preparation

化学 色谱法 药品 校准曲线 校准 定量分析(化学) 样品制备 分析化学(期刊) 检出限 药理学 数学 统计 医学
作者
Niluka De Mel,Sri Hari Raju Mulagapati,Mingyan Cao,Dengfeng Liu
出处
期刊:Journal of Chromatography B [Elsevier BV]
卷期号:1116: 51-59 被引量:3
标识
DOI:10.1016/j.jchromb.2019.04.012
摘要

Residual free-drug–related species that are present in antibody-drug conjugates (ADC) are a potential safety risk to patients and are therefore categorized as a critical quality attribute that must be strictly monitored and controlled. Among the many analytical methods developed for free-drug analysis, reversed-phase liquid chromatography (RP-LC) is the most common approach. Conventional RP-LC methods for free-drug analysis, however, involve labor-intensive sample preparation. Here we present a new RP-LC method to directly analyze free-drug–related species in an ADC sample without the need for sample preparation. In our work, free-drug–related species were very well separated from ADC peaks in the chromatography gradient. Typical performance issues observed in conventional RP-LC, such as column fouling, detection interference, and carryover, were not observed or were negligible with this new method. Three options were evaluated for free-drug quantitation: Strohl (2017) [1] use of an external free drug calibration curve for determination of absolute concentration; Perez et al. (2014) [2] calculation of relative percentage based on peak area ratio between free drug and ADC at a characteristic wavelength unique for drug payload; and (Beck et al., 2017) [3] calculation of relative percentage based on peak area ratio between free drug and corrected ADC peak area (at any wavelength). The method with calibration curve provides the highest sensitivity, the best accuracy and precision for determination of free drug present in the ADC. However, the second and third options were simpler because they eliminated the need for an external calibration curve, making them worth exploring. Due to its simplicity and compatibility with mass spectrometry, the new method is also a good choice for direct analysis of stability samples.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
子琢发布了新的文献求助10
刚刚
jyy应助大豹子采纳,获得10
刚刚
1秒前
博士后完成签到 ,获得积分10
1秒前
1秒前
2秒前
呵呵呵完成签到,获得积分10
3秒前
栗子完成签到,获得积分10
4秒前
yellowonion发布了新的文献求助10
6秒前
诸葛御风应助jia采纳,获得50
7秒前
yaoqi完成签到,获得积分10
7秒前
安小野发布了新的文献求助10
8秒前
故酒应助Why采纳,获得10
9秒前
9秒前
酷炫的春天完成签到,获得积分10
10秒前
11秒前
黄鑫涛完成签到,获得积分10
12秒前
深情的寒风完成签到,获得积分20
12秒前
无尘发布了新的文献求助10
14秒前
生动的煎蛋完成签到 ,获得积分10
14秒前
wanjingwan完成签到 ,获得积分10
15秒前
Sly关闭了Sly文献求助
16秒前
17秒前
17秒前
今后应助yimeng采纳,获得10
18秒前
老迟到的芹菜完成签到,获得积分10
18秒前
20秒前
西西西完成签到,获得积分10
20秒前
21秒前
21秒前
mickiller发布了新的文献求助10
22秒前
yzg关注了科研通微信公众号
22秒前
陈皮发布了新的文献求助10
22秒前
DDDD发布了新的文献求助10
23秒前
可爱的函函应助无尘采纳,获得10
23秒前
yc发布了新的文献求助10
23秒前
CipherSage应助老迟到的芹菜采纳,获得10
24秒前
24秒前
上官若男应助科研通管家采纳,获得10
24秒前
彭于晏应助科研通管家采纳,获得10
24秒前
高分求助中
Les Mantodea de Guyane Insecta, Polyneoptera 2500
Technologies supporting mass customization of apparel: A pilot project 600
Introduction to Strong Mixing Conditions Volumes 1-3 500
China—Art—Modernity: A Critical Introduction to Chinese Visual Expression from the Beginning of the Twentieth Century to the Present Day 430
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
China Gadabouts: New Frontiers of Humanitarian Nursing, 1941–51 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3796344
求助须知:如何正确求助?哪些是违规求助? 3341452
关于积分的说明 10306338
捐赠科研通 3057993
什么是DOI,文献DOI怎么找? 1678019
邀请新用户注册赠送积分活动 805746
科研通“疑难数据库(出版商)”最低求助积分说明 762799