Impact of Interferences Including Metabolite Crossreactivity on Therapeutic Drug Monitoring Results
Impact of Interferences Including Metabolite Crossreactivity on Therapeutic Drug Monitoring Results
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DOI：
10.1097/ftd.0b013e318261c2c9
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发表时间：
2012-10-01
影响因子：
2.5
通讯作者：
Dasgupta, Amitava
中科院分区：
文献类型：
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作者：
Dasgupta, Amitava
治疗药物监测是毒理学实验室提供的服务的一个组成部分，因为某些药物需要进行剂量调整的常规监测，以实现最佳治疗反应并避免药物不良反应。免疫测定广泛用于治疗药物监测。然而，免疫测定受到外源性和内源性化合物（包括母体药物的代谢物）的干扰。地高辛免疫测定法比用于治疗药物监测的任何其他免疫测定法更常受到影响。地高辛免疫测定受内源性地高辛样免疫反应性物质和外源性化合物（如各种药物、某些草药补充剂和Digibind）的影响。卡马西平代谢为10，11-环氧化物，该代谢物与卡马西平免疫测定的交叉反应性可在0%至94%之间变化。用于测量三环类抗抑郁药浓度的免疫测定受三环类抗抑郁药代谢物和许多其他药物的影响。免疫抑制剂的免疫测定也受到代谢物的显著干扰，建议将液相色谱法与质谱法或串联质谱法结合用于免疫抑制剂的治疗药物监测。然而，液相色谱与质谱联用也可能受到干扰，例如，由于离子抑制或来自同量异位素离子。
Therapeutic drug monitoring is an integral part of services offered by toxicology laboratories because certain drugs require routine monitoring for dosage adjustment to achieve optimal therapeutic response and avoid adverse drug reactions. Immunoassays are widely used for therapeutic drug monitoring. However, immunoassays suffer from interferences from both exogenous and endogenous compounds including metabolites of the parent drug. Digoxin immunoassays are affected more commonly than any other immunoassays used for therapeutic drug monitoring. Digoxin immunoassays are affected by endogenous digoxin-like immunoreactive substances and exogenous compounds such as various drugs, certain herbal supplements, and Digibind. Carbamazepine is metabolized to carbamazepine 10, 11-epoxide, and the crossreactivity of this metabolite with carbamazepine immunoassay may vary from 0% to 94%. Immunoassays used for measuring concentrations of tricyclic antidepressants are affected by tricyclic antidepressant metabolites and by a number of other drugs. Immunoassays for immunosuppressants are also subjected to significant interferences from metabolites, and liquid chromatography combined with mass spectrometry or tandem mass spectrometry is recommended for therapeutic drug monitoring of immunosuppressants. However, liquid chromatography combined with mass spectrometry may also suffer from interferences, for example, due to ion suppression or from isobaric ions.