Department of Electrical Engineering and Electronics, University of Liverpool, Liverpool, L69 3GJ, UK.
Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK.
BMC Med. 2024 Nov 25;22(1):553. doi: 10.1186/s12916-024-03776-3.
Paracetamol is the most consumed medicine globally. Its accessibility contributes to common overdose. Paracetamol overdose is responsible for > 50% of acute liver failure cases, making it the second most common reason for a liver transplant. Rapid quantitation of paracetamol is crucial to guide treatment of paracetamol overdose. Current tests require invasive sampling and relatively long turnaround times. Paper arrow-mass spectrometry (PA-MS) combines sample collection, extraction, separation, enrichment and ionisation onto a single paper strip, achieving rapid, accurate, cost-effective and eco-friendly analysis direct from raw human saliva.
To validate PA-MS against an established test, 17 healthy adults were recruited. Samples were collected before and at 15, 30, 60, 120 and 240 min after ingesting 1 g of paracetamol. Plasma measured with an established clinical test served as the reference standard to validate PA-MS with three biofluids-plasma, resting saliva (RS) and stimulated saliva (SS). Participants' views of blood, RS and SS sampling procedures were assessed qualitatively. Cross-validation was assessed using Lin's concordance correlation coefficients (CCC), Bland-Altman difference plots, and ratios of PA-MS to the reference standard test.
PA-MS using stimulated saliva offers a reliable alternative to intravenous blood sampling. The CCC is 0.93, the mean difference with the reference test is - 0.14 mg/L, and the ratios compared to the reference test are 0.84-1.27 from correlated samples collected at 5 intervals over 4 h for each participant.
Paracetamol detection from SS with PA-MS provides a reliable result that can aid timely treatment decisions. Differences between paracetamol concentration in resting and stimulated saliva were also identified for the first time, highlighting the importance of standardising saliva collection methods in general. This study marks a major milestone towards rapid and convenient saliva analysis.
对乙酰氨基酚是全球应用最广泛的药物。其普及性导致了常见的用药过量。对乙酰氨基酚过量是导致急性肝衰竭病例的主要原因，超过 50%，是肝移植的第二大常见原因。快速定量对乙酰氨基酚对于指导对乙酰氨基酚过量的治疗至关重要。目前的检测方法需要有创采样和相对较长的周转时间。纸箭头质谱法（PA-MS）将样品采集、提取、分离、富集和离子化在一个纸条上，实现了从原始人唾液中快速、准确、经济高效和环保的分析。
为了验证 PA-MS 与既定测试的相关性，招募了 17 名健康成年人。在摄入 1g 对乙酰氨基酚之前和之后的 15、30、60、120 和 240 分钟收集了样本。使用既定的临床测试测量的血浆被用作参考标准，通过三种生物流体-血浆、静止唾液（RS）和刺激唾液（SS）来验证 PA-MS。定性评估参与者对血液、RS 和 SS 采样程序的看法。使用 Lin 的一致性相关系数（CCC）、Bland-Altman 差异图和 PA-MS 与参考标准测试的比值进行交叉验证。
使用刺激唾液的 PA-MS 为静脉血采样提供了可靠的替代方法。CCC 为 0.93，与参考测试的平均差值为-0.14mg/L，在 4 小时内的 5 个时间点上，从相关样本中比较到参考测试的比值为 0.84-1.27。
PA-MS 从 SS 中检测对乙酰氨基酚可以提供可靠的结果，有助于及时做出治疗决策。还首次发现了 RS 和 SS 中对乙酰氨基酚浓度之间的差异，突出了一般情况下标准化唾液收集方法的重要性。这项研究标志着快速便捷的唾液分析迈出了重要的一步。
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