Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, 80045, USA.
Anal Bioanal Chem. 2022 May;414(11):3387-3395. doi: 10.1007/s00216-022-03954-3. Epub 2022 Feb 15.
HIV prevention and treatment with injectable cabotegravir and/or rilpivirine administered once every 4 to 8 weeks is an attractive alternative to daily therapy. Prescribed dosage and drug concentrations in plasma are based on patient data collected in clinical trials, but actual patients are expected to exhibit more variability in drug concentrations, which is important to quantify. Here, we demonstrate the first quantitative point-of-care assay with a miniature mass spectrometer to assess these drug concentrations in whole blood. Quantitative performance is obtained using paper spray ionization in combination with tandem mass spectrometry (MS/MS) in the clinically relevant concentration range of both drugs. Limits of quantitation (LoQs) of cabotegravir and rilpivirine are measured to be 750 ng/mL and 20 ng/mL, respectively. The assay turnaround time is < 4 min, and strong linear relationships are established between MS/MS responses and concentration, with percentage of relative standard deviations (RSDs) that are <15% at concentrations above the LoQs. The speed, portability, low power consumption, and specificity offered by the miniature instrument should make it an appropriate platform for measuring drug concentrations in a walk-in clinic using small volumes of patient blood.
每 4 至 8 周注射一次卡替拉韦和/或利匹韦林进行 HIV 预防和治疗,是一种有吸引力的替代每日治疗的方法。在临床试验中根据患者数据来规定注射剂量和血浆中的药物浓度,但实际患者的药物浓度预计会有更大的变化,这一点很重要,需要定量分析。在这里,我们展示了第一个使用微型质谱仪进行即时检测的定量分析方法,用于评估全血中的这些药物浓度。使用纸喷雾电离与串联质谱(MS/MS)相结合,在两种药物的临床相关浓度范围内获得定量性能。卡替拉韦和利匹韦林的定量下限(LoQ)分别测量为 750ng/mL 和 20ng/mL。检测时间<4 分钟,并且在 LoQ 以上的浓度下,MS/MS 响应与浓度之间建立了强烈的线性关系,相对标准偏差(RSD)的百分比<15%。该微型仪器具有速度快、便携性强、功耗低和特异性高的特点,有望成为在门诊使用小体积患者血液进行药物浓度测量的合适平台。