Saatchi A, Zarkovic T M, Borden S A, Palaty J, Gill C G
Applied Environmental Research Laboratories, Department of Chemistry, Vancouver Island University, Nanaimo, BC, Canada.
Department of Chemistry, University of Victoria, Victoria, BC, Canada.
J Mass Spectrom Adv Clin Lab. 2024 Feb 15;32:41-46. doi: 10.1016/j.jmsacl.2024.02.003. eCollection 2024 Apr.
Monitoring the atypical antipsychotic drug clozapine is crucial to ensure patient safety. This article showcases a high-throughput analytical method for measuring clozapine and its primary metabolite norclozapine (N-desmethylclozapine) in serum using paper spray mass spectrometry (PS-MS).
This study aimed to assess the viability of a PS-MS method for the rapid measurement of clozapine and norclozapine in human serum samples as an alternative to liquid chromatography mass spectrometry (LC-MS).
Serum samples were processed by protein precipitation followed by deposition of the supernatant containing labelled internal standards onto paper spray substrates mounted in cartridges. Analytes were then analyzed using a triple quadrupole mass spectrometer equipped with a commercial paper spray ionization source. The results obtained from the patient samples were compared to those from a validated LC-MS assay.
PS-MS calibrations for clozapine and norclozapine were linear (R > 0.99) over five days. Between-run precision was below 8 %, and within-run precision did not exceed 10 %. When compared to a validated LC-MS method, the mean bias for 39 patient samples was -9% for clozapine and -1% for norclozapine, with no outliers. Mass spectrometry ion ratio comparisons indicated no interference for patient samples above the lower limit of quantification. There was less than 7 % change in the measured concentrations of both analytes over five days for samples dried on paper substrates. Notably, virtually no maintenance of the MS source was required during this study.
This study illustrates the potential of PS-MS for serum drug monitoring in the clinical laboratory.
监测非典型抗精神病药物氯氮平对于确保患者安全至关重要。本文展示了一种使用纸喷雾质谱法（PS-MS）测量血清中氯氮平和其主要代谢物去甲氯氮平（N-去甲基氯氮平）的高通量分析方法。
本研究旨在评估PS-MS方法作为液相色谱质谱法（LC-MS）的替代方法用于快速测量人血清样本中氯氮平和去甲氯氮平的可行性。
血清样本通过蛋白沉淀进行处理，然后将含有标记内标的上清液沉积到安装在小柱中的纸喷雾基质上。然后使用配备商业纸喷雾电离源的三重四极杆质谱仪分析分析物。将患者样本获得的结果与经过验证的LC-MS测定结果进行比较。
氯氮平和去甲氯氮平的PS-MS校准在五天内呈线性（R>0.99）。批间精密度低于8%，批内精密度不超过10%。与经过验证的LC-MS方法相比，39例患者样本中氯氮平的平均偏差为-9%，去甲氯氮平为-1%，无异常值。质谱离子比比较表明，高于定量下限的患者样本无干扰。对于在纸质基质上干燥的样本，两种分析物的测量浓度在五天内变化小于7%。值得注意的是，在本研究期间几乎不需要维护质谱源。
本研究说明了PS-MS在临床实验室血清药物监测中的潜力。
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