患者及其亲属尿液和毛发中碳酸酐酶抑制剂及其代谢物的定量分析。
Quantification of Carbonic Anhydrase Inhibitors and Metabolites in Urine and Hair of Patients and Their Relatives.
作者信息
Lo Faro Alfredo Fabrizio, Tini Anastasio, Bambagiotti Giulia, Pirani Filippo, Faragalli Andrea, Carle Flavia, Pacella Elena, Ceka Artan, Moretti Marco, Gottardi Massimo, Lassandro Nicola Vito, Nicolai Michele, Lupidi Marco, Mariotti Cesare, Busardò Francesco Paolo, Carlier Jeremy
机构信息
Unit of Forensic Toxicology, Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Via Tronto 10/a, 60126 Ancona, AN, Italy.
Center of Epidemiology Biostatistics and Information Technology, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Via Tronto 10/a, 60126 Ancona, AN, Italy.
出版信息
Biology (Basel). 2022 Sep 21;11(10):1379. doi: 10.3390/biology11101379.
Carbonic anhydrase inhibitors (CAIs) are prescription drugs also used in doping to dilute urine samples and tamper with urinalyses. Dorzolamide, brinzolamide, and acetazolamide are prohibited by the World Anti-Doping Agency. Detecting CAIs and their metabolites in biological samples is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment for ocular hypertension or glaucoma. Samples of the patients' relatives were analyzed to assess potential for accidental exposure. After washing, 25 mg hair was incubated with an acidic buffer at 100 °C for 1 h. After cooling and centrifugation, the supernatant was analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urine (100 μL) was diluted and centrifuged before UHPLC-MS/MS analysis. Run time was 8 min through a reverse-phase column with a mobile phase gradient. MS/MS analysis was performed in a multiple-reaction monitoring mode after positive electrospray ionization. Median urinary concentration was 245 ng/mL (IQR: 116.2-501 ng/mL) for dorzolamide, 81.1 ng/mL (IQR: 35.9-125.3 ng/mL) for -deethyl-dorzolamide, 0.77 ng/mL (IQR: 0.64 ng/mL-0.84 ng/mL) for -acetyl-dorzolamide, 38.9 ng/mL (IQR: 20.4-79.2 ng/mL) for brinzolamide, and 72.8 ng/mL (IQR: 20.7-437.3 ng/mL) for acetazolamide. Median hair concentration was 0.48 ng/mg (IQR: 0.1-0.98 ng/mg) for dorzolamide, 0.07 ng/mg (IQR: 0.06-0.08 ng/mg) for -deethyl-dorzolamide, 0.40 ng/mL (IQR: 0.13-1.95 ng/mL) for brinzolamide. Acetazolamide was detected in only one hair sample. Dorzolamide and brinzolamide were detected in the urine of three and one relatives, respectively. Cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. We reported the first concentrations of brinzolamide in hair.
碳酸酐酶抑制剂（CAIs）是一类处方药，也被用于兴奋剂领域以稀释尿液样本并干扰尿液分析。多佐胺、布林佐胺和乙酰唑胺被世界反兴奋剂机构禁止使用。在生物样本中检测CAIs及其代谢物对于记录兴奋剂滥用情况至关重要。我们对88名接受高眼压症或青光眼治疗的患者的尿液和毛发中的多佐胺、布林佐胺、乙酰唑胺及其代谢物进行了定量分析。对患者亲属的样本进行分析以评估意外接触的可能性。清洗后，将25mg毛发在100°C的酸性缓冲液中孵育1小时。冷却并离心后，通过超高效液相色谱 - 串联质谱法（UHPLC - MS/MS）分析上清液。尿液（100μL）在进行UHPLC - MS/MS分析前进行稀释和离心。通过带有流动相梯度的反相柱的运行时间为8分钟。在正电喷雾电离后，以多反应监测模式进行MS/MS分析。多佐胺的尿中浓度中位数为245ng/mL（四分位间距：116.2 - 501ng/mL），去乙基多佐胺为81.1ng/mL（四分位间距：35.9 - 125.3ng/mL），乙酰多佐胺为0.77ng/mL（四分位间距：0.64ng/mL - 0.84ng/mL），布林佐胺为38.9ng/mL（四分位间距：20.4 - 79.2ng/mL），乙酰唑胺为72.8ng/mL（四分位间距：20.7 - 437.3ng/mL）。多佐胺的毛发浓度中位数为0.48ng/mg（四分位间距：0.1 - 0.98ng/mg），去乙基多佐胺为0.07ng/mg（四分位间距：0.06 - 0.08ng/mg），布林佐胺为0.40ng/mL（四分位间距：0.13 - 1.95ng/mL）。仅在一个毛发样本中检测到乙酰唑胺。在三名和一名亲属的尿液中分别检测到多佐胺和布林佐胺。为避免因污染或被动接触导致假阳性，需要确定尿中多佐胺和布林佐胺的截断浓度。我们报告了毛发中布林佐胺的首批浓度数据。
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