Indinavir (IDV) is a potent and well-tolerated protease inhibitor antiretroviral (ARV) drug used as a component of the highly active antiretroviral therapy (HAART) of human immunodeficiency virus (HIV). It undergoes hepatic first-pass metabolism that is catalysed by microsomal cytochrome P450-3A4 enzyme (CYP3A4), which results in pharmacokinetics that may be favourable or adverse. Therapeutic drug monitoring (TDM) of IDV during HIV treatment is therefore critical, in order to prevent the adverse effects of its first-pass metabolism and optimise an individual’s dosage regime. Biosensors are now the preferred diagnostic tools for TDM assessment at point-of-care, due to their high sensitivity and real-time response. An electrochemical biosensor for IDV was prepared by depositing a thin film of CYP3A4 (a thiolate enzyme) and thioglycolic acid-capped palladium telluride quantum dot (TGA-PdTeQD) on a cysteamine-functionalised gold disk electrode (Cyst|Au) using a combination of thiol and carbodiimide covalent bonding chemistries. The electrochemical signatures of the biosensor (CYP3A4|TGA-PdTeQD|Cyst|Au) were determined by cyclic voltammetry (CV) that was performed at a scan rate of 500 mV s⁻¹, and the sensor responses at the characteristic reduction peak potential value of − 0.26 V were recorded. The sensitivity, linear range (LR) and limit of detection (LOD) values of the indinavir biosensor were 4.45 ± 0.11 μA nM⁻¹ IDV, 0.5–1.0 nM IDV (i.e. 3.6 × 10⁻⁴–7.1 × 10⁻⁴ mg L⁻¹ IDV) and 4.5 × 10⁻⁴ mg L⁻¹ IDV, respectively. The values of the two analytical parameters (LR and LOD) of the biosensor were by up to four orders of magnitude lower than the maximum plasma concentration (C_max) values of indinavir (0.13–8.6 mg L⁻¹ IDV). The IDV biosensor was successfully used to detect IDV in human serum samples containing dissolved indinavir tablet. This, therefore, indicates the indinavir biosensor’s suitability for TDM applications, using samples obtained within 1–2 h of drug intake at point-of-care, for which very low levels of the drug are expected.

中文翻译：

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用于艾滋病毒药物的生物相容性碲化钯量子点放大生物传感器

茚地那韦（IDV）是一种有效且耐受性良好的蛋白酶抑制剂抗逆转录病毒（ARV）药物，被用作人类免疫缺陷病毒（HIV）的高效抗逆转录病毒疗法（HAART）的组成部分。它经历了微粒体细胞色素P450-3A4酶（CYP3A4）催化的肝首过代谢，其药代动力学可能是有利的也可能是不利的。因此，在HIV治疗过程中IDV的治疗药物监测（TDM）至关重要，以防止其首过代谢的不良影响并优化个体的用药方案。现在，由于生物传感器具有高灵敏度和实时响应，因此它们是在现场即时医疗（TDM）评估中首选的诊断工具。通过将CYP3A4（硫醇盐酶）和巯基乙酸封端的碲化钯量子点（TGA-PdTeQD）薄膜沉积在半胱胺官能化的金圆盘电极（Cyst | Au）上，制备出IDV电化学生物传感器。硫醇和碳二亚胺的共价键合化学。通过循环伏安法（CV）确定生物传感器（CYP3A4 | TGA-PdTeQD | Cyst | Au）的电化学特征，该循环伏安法以500 mV s的扫描速率进行^-1，并且记录了在特性降低峰值电势值为-0.26 V时的传感器响应。茚地那韦生物传感器的灵敏度，线性范围（LR）和检测极限（LOD）值分别为4.45±0.11μAnM ^-1 IDV，0.5–1.0 nM IDV（即3.6×10 ^-4 –7.1×10 ^-4 mg L ^-1 IDV）和4.5×10 ^-4 mg L ^-1 IDV。生物传感器的两个分析参数（LR和LOD）值比茚地那韦（0.13–8.6 mg L）的最大血浆浓度（C _max）值低多达四个数量级。^-1 IDV）。IDV生物传感器已成功用于检测含有溶解的茚地那韦片剂的人血清样品中的IDV。因此，这表明茚地那韦生物传感器适用于TDM应用，使用的是在现场即时服药后1-2小时内获得的样品，预计药物的水平非常低。