Identification of the aromatase inhibitors anastrozole and exemestane in human urine using liquid chromatography/tandem mass spectrometry

Mareck, Ute; Geyer, Hans; Guddat, Sven; Haenelt, Nadine; Koch, Anja; Kohler, Maxie; Opfermann, Georg; Thevis, Mario; Schänzer, Wilhelm

doi:10.1002/rcm.2545

Cited by 48 publications

(34 citation statements)

References 19 publications

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“…The method employed a mobile phase consisting of ACN:water containing N,Ndimethyloctylamine (pH adjusted to 3.0 with orthophosphoric acid) at a flow rate of 1.0 ml/min with an injection volume of 20 µl, monitored at 270 Omeprozole LC-MS/MS [30] Androsteroneglucuronide LC-MS/MS [41] Letrozole LC-MS/MS [43] Bunitrolol LC-MS/MS [44] ANA-d12 LC-MS/MS [45] Desmethyldiazepam LC-MS/MS [18,21] Verapamil LC-MS/MS [34] Diazepam GC-ECD [46,47] Clomipramine GC-FID [35] LC-MS/MS= LC coupled with tandem mass spectrometry; GC-ECD= GC with electron capture detection; GC-FID= gas chromatography with flame ionization detection; ANA-d12= deuterium-labeled anastrozole.…”

Section: Uv Detectionmentioning

confidence: 99%

“…An LC-MS/MS method for the simultaneous detection of ANA and exemestane in human urine using liquid-liquid extraction with a low LOQ for ANA has been reported [41] . Samples were analyzed via LC coupled to triple quadrupole mass spectrometer using APCI on an RP 18 column (4×55 mm, 3 µm).…”

Section: Liquid Chromatography Mass Spectrometrymentioning

confidence: 99%

“…Nevertheless, due to its high cost, this method would be more suitable for the determination of ANA and exemestane levels in situations where blood sample collection is not feasible. A common example is the screening of athletes for some selected anabolic androgenic steroids [41] .…”

Section: Liquid Chromatography Mass Spectrometrymentioning

confidence: 99%

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A Review of Chromatographic Methods Used in the Determination of Anastrozole Levels

Abubakar

Gan

2016

Indian J Pharm Sci

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Owing to the efficacy and popularity of anastrozole in the treatment of estrogen receptor-positive breast cancer, interest in analytical methods for its quantitative measurement both in pharmaceutical dosage formulations and Biological samples has risen sharply for a decade. This paper reviews the existing chromatographic methods, which are based on two popular detection methods: high performance liquid chromatography and gas chromatography mass spectrometry. The Current high performance liquid chromatography methods with UV detection so far reported; focus primarily on determining the concentration of anastrozole in pharmaceutical dosage formulations. However, such methods are insufficient in measuring the concentrations yielded in biological samples when the relatively low doses (1 mg daily) recommended for breast cancer treatment are used. Therefore, there is limited applicability of HPLC-UV detection methods for quantitative measurements of anastrozole in biological samples. A number of methods combining liquid chromatography with tandem mass spectrometry with limits of quantitation as low as 0.05 ng/ml have been developed for anastrozole measurement in plasma. A few methods on active pharmaceutical ingredients have also been reported. On the other hand, only a few gas chromatography methods have successfully been developed for the determination of anastrozole concentrations. In majority of the methods, where relevant, parameters such as selectivity, linearity, limit of detection, limit of quantitation, and accuracy have been considered, and recovery assessments during accuracy evaluation are generally satisfactory, with reported values ranging between 81 and 109%. However, a significant number of these studies did not use an internal standard to correct for the area of anastrozole, making their accuracies questionable. Overall, the current available detection methods for anastrozole are inadequate, and improved method validation techniques as well as simple and affordable anastrozole quantification methods in both pharmaceutical dosage formulations and especially biological samples are needed.

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Section: Uv Detectionmentioning

confidence: 99%

Section: Liquid Chromatography Mass Spectrometrymentioning

confidence: 99%

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A Review of Chromatographic Methods Used in the Determination of Anastrozole Levels

Abubakar

Gan

2016

Indian J Pharm Sci

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“…One possible approach is to use a biomarker such as plasma or urine drug or metabolite levels to determine hormonal treatment adherence. 14,18 Athletes use aromatase inhibitors to reverse or prevent gynecomastia, an adverse effect of certain performanceenhancing anabolic androgenic steroids. 18 In response to a growing underground movement of aromatase inhibitor misuse, the International Olympic Committee and the World Anti-Doping Agency added hormone antagonists and modulators to their list of prohibited substances.…”

Section: Introductionmentioning

confidence: 99%

“…14,18 Athletes use aromatase inhibitors to reverse or prevent gynecomastia, an adverse effect of certain performanceenhancing anabolic androgenic steroids. 18 In response to a growing underground movement of aromatase inhibitor misuse, the International Olympic Committee and the World Anti-Doping Agency added hormone antagonists and modulators to their list of prohibited substances. 19 As a result, assays for these substances are commercially available through World Anti-Doping Agency-approved laboratories around the world.…”

Section: Introductionmentioning

confidence: 99%

Use of a Urine Anastrozole Assay to Determine Treatment Discontinuation Among Women With Hormone-Sensitive Breast Cancer: A Pilot Study

Hillyer

Neugut²,

Crew³

et al. 2012

JOP

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Purpose: Multiple studies have shown that adherence to adjuvant hormonal therapy in women with breast cancer is suboptimal. Measurements of compliance with self-report, pill counts, and/or pharmacy records are susceptible to bias. We assessed the feasibility of using a urine anastrozole assay as an objective biomarker of nonadherence to anastrozole treatment. Patients and Methods:We recruited consecutive postmenopausal women, age Ն 18 years, with hormone-sensitive nonmetastatic breast cancer who were prescribed anastrozole at least 3 months before enrollment. Each completed a short survey to gather information on demographics, anastrozole compliance history, and self-reported medication history, tumor characteristics, and treatment received. A single, random 15-mL urine sample was collected and tested for the presence of anastrozole using a previously validated assay. Patients were told they were part of a study to determine if anastrozole could be detected in the urine.Results: Among 96 participants, mean age was 63.7 years (range, 51 to 70 years). The population was diverse, with 56.5% white, 57.6% US born, 59.8% unemployed, and 56.6% college educated. Prior treatment included chemotherapy (50%) and/or radiotherapy (58.7%). Mean duration of anastrozole treatment was 2.2 years (standard deviation, 1.6). Four participants reported nonadherence and declined to submit urine samples, and two had no detectable level of anastrozole (six of 96; 6.3%). Detectable levels among adherent women ranged from 49.3 to 632.8 ng/mL. Conclusion:We demonstrated that collection of urine to measure anastrozole levels is feasible and reliable. Identifying biomarkers to measure adherence is critical for studies investigating interventions to improve hormonal therapy compliance.

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Modern Mass Spectrometry‐Based Analytical Assays

Thevis

2010

Mass Spectrometry in Sports Drug Testing

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Identification of the aromatase inhibitors anastrozole and exemestane in human urine using liquid chromatography/tandem mass spectrometry

Cited by 48 publications

References 19 publications

A Review of Chromatographic Methods Used in the Determination of Anastrozole Levels

A Review of Chromatographic Methods Used in the Determination of Anastrozole Levels

Use of a Urine Anastrozole Assay to Determine Treatment Discontinuation Among Women With Hormone-Sensitive Breast Cancer: A Pilot Study

Modern Mass Spectrometry‐Based Analytical Assays

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