Interference of endogenous components present in biological fluids has a profound effect on the performance of LC–MS/MS-based assays. The present work evaluates the effect of plasma matrix components during sample preparation for accurate and precise determination of valsartan, clindamycin and mesalamine by LC–ESI–MS/MS. The methods were thoroughly assessed using different approaches for sample preparation such as solid-phase extraction (SPE) with different cartridges for valsartan, conventional protein precipitation and Phree phospholipid removal cartridge for clindamycin and liquid–liquid extraction (LLE) with and without derivatization for mesalamine to minimize matrix interference. The extent of matrix effect was determined by post-column analyte infusion, post-extraction spike method and by calculation of slope of calibration lines for different plasma sources. The influence of matrix ion suppression/enhancement on the extraction recovery and sensitivity of the methods was identified and quantified. The mean recovery obtained was 96.8% for valsartan using SPE on Oasis MCX, 92.2% for clindamycin using Phree phospholipid cartridge and 96.5% for mesalamine using LLE following derivatization. The intra-batch and inter-day precision (% CV) was ˂4.0 for the methods and was validated as per the current regulatory guidance.

存在于生物液体中的内源性成分的干扰对基于LC-MS / MS的检测方法的性能产生了深远的影响。本工作评估了样品制备过程中血浆基质成分对通过LC-ESI-MS / MS准确而精确地测定缬沙坦，克林霉素和美沙拉敏的影响。使用不同的样品制备方法对方法进行了彻底的评估，例如采用固相萃取（SPE）的缬沙坦药筒，常规蛋白质沉淀法和用于克林霉素的Phree磷脂去除药筒以及采用和不采用美沙拉敏衍生化的液-液萃取（LLE）最小化矩阵干扰。柱后分析物的注入确定了基质效应的程度，萃取后加标方法和通过计算不同等离子源的校准线的斜率。鉴定并定量了基质离子抑制/增强方法对提取回收率和灵敏度的影响。衍生化后，在Oasis MCX上使用SPE进行缬沙坦回收的平均回收率为96.8％，使用Phree磷脂色谱柱对克林霉素回收的回收率为92.2％，对于使用LLE的美沙明胺回收的回收率为96.5％。该方法的批内精度和日间精度（％CV）为˂4.0，并已根据当前的监管指南进行了验证。衍生化后，使用Phree磷脂小柱测定的克林霉素含量为2％，使用LLE测定的美沙拉敏含量为96.5％。该方法的批内精度和日间精度（％CV）为˂4.0，并已根据当前的监管指南进行了验证。衍生后，使用Phree磷脂小柱对克林霉素的投药量为2％，对美沙明胺的LLE为96.5％。该方法的批内精度和日间精度（％CV）为˂4.0，并已根据当前的监管指南进行了验证。