Buckley Tiffany, Kitchen Christopher, Vyas Gopal, Siegfried Nathan A, Tefera Eshetu, Chen Shuo, DiPaula Bethany A, Kelly Deanna L
Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland.
University of Maryland School of Medicine, Maryland Psychiatric Research Center, Baltimore, Maryland; and.
Ther Drug Monit. 2020 Oct;42(5):771-777. doi: 10.1097/FTD.0000000000000777.
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. Although serum clozapine levels can help guide treatment, they are underutilized owing to requirements for frequent venous blood draws and lack of immediate results.
Clozapine levels measured with a novel immunoassay technology (which enables point-of-care development) were compared with those measured by standard liquid chromatography/tandem mass spectrometry (LC-MS/MS). Frozen serum aliquots of 117 samples (N = 48 patients with schizophrenia on clozapine; N = 24 patients with schizophrenia not on clozapine; N = 45 healthy controls) were sent to a national reference laboratory (NRL) for clozapine level determination by LC-MS/MS, and matching samples were subjected to novel immunoassay (3 runs). At a later date, another frozen aliquot from the same date was sent to the NRL for repeat testing.
The NRL obtained 18 false-positive clozapine results (mean 42.39 ± 32.06, range 21-159 ng/mL) in participants not on clozapine (N = 3) and healthy controls (N = 15). The immunoassay showed no false-positive clozapine results. The clozapine levels were correlated between both assays (r = 0.84, P < 0.0001), despite 16% higher clozapine levels with immunoassay (482.08 ± 270.88 ng/mL immunoassay, 414.98 ± 186.29 ng/mL LC-MS/MS [P = 0.03]). Agreement analysis using concordance correlation coefficient (CCC) for LC-MS/MS of the 2 aliquots yielded CCC = 0.869; 95% confidence interval = 0.690-0.970, whereas higher agreement results were observed for the 3 runs of immunoassay (CCC = 0.99; 95% confidence interval = 0.979-0.997).
The lack of false positives observed with immunoassay, higher repeat performance agreement, and good correlation with LC-MS/MS may indicate the more robust performance of immunoassay than that of LC-MS/MS clozapine-level determination.
氯氮平是治疗难治性精神分裂症最有效的抗精神病药物。尽管血清氯氮平水平有助于指导治疗，但由于需要频繁采集静脉血且无法立即得到结果，这些指标未得到充分利用。
将采用新型免疫分析技术（可实现即时检测）测定的氯氮平水平与通过标准液相色谱/串联质谱法（LC-MS/MS）测定的水平进行比较。将117份样本（N = 48例服用氯氮平的精神分裂症患者；N = 24例未服用氯氮平的精神分裂症患者；N = 45名健康对照）的冷冻血清等分试样送至国家参考实验室（NRL），通过LC-MS/MS测定氯氮平水平，并对匹配样本进行新型免疫分析（3次检测）。之后，将同一天的另一份冷冻等分试样送至NRL进行重复检测。
NRL在未服用氯氮平的参与者（N = 3）和健康对照（N = 15）中获得了18例假阳性氯氮平结果（平均42.39±32.06，范围21 - 159 ng/mL）。免疫分析未显示氯氮平假阳性结果。两种检测方法的氯氮平水平具有相关性（r = 0.84，P < 0.0001），尽管免疫分析的氯氮平水平高16%（免疫分析为482.08±270.88 ng/mL，LC-MS/MS为414.98±186.29 ng/mL [P = 0.03]）。对两份等分试样的LC-MS/MS使用一致性相关系数（CCC）进行一致性分析，得出CCC = 0.869；95%置信区间 = 0.690 - 0.970，而免疫分析的3次检测结果一致性更高（CCC = 0.99；95%置信区间 = 0.979 - 0.997）。
免疫分析未观察到假阳性结果、更高的重复性能一致性以及与LC-MS/MS的良好相关性，这可能表明免疫分析在氯氮平水平测定方面的性能比LC-MS/MS更可靠。
