Evaluation of a LC–MS method for everolimus preclinical determination in brain by using [13C2D4]RAD001 internal standard

Giovagnoli, Stefano; Cassano, Tommaso; Pace, Lorenzo; Magini, Alessandro; Polchi, Alice; Tancini, Brunella; Perluigi, Marzia; Marco, Federico De; Emiliani, Carla; Dolcetta, Diego

doi:10.1016/j.jchromb.2015.01.035

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…The solid-phase extraction (SPE) and organic solvent extraction preparation methods for precipitated proteins (PP) reported previously have lower detection limits or lower recoveries than the pretreatment methods in this study for MMF, FK-506, RAPA, PIM, MPA and EVER [33][34][35][36]. Compared with whole blood, cerebrospinal fluid is more difficult to collect in experiments, so our matrix used human whole blood [37]. The current method is characterized by increased sensitivity and recovery advantage compared with the previously published methods.…”

Section: Comparisons With Other Methodsmentioning

confidence: 99%

Simultaneous Determination of Six Immunosuppressants in Human Whole Blood by HPLC-MS/MS Using a Modified QuEChERS Method

et al. 2022

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A high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of mycophenolic acid, mycophenolate mofetil, tacrolimus, rapamycin, everolimus and pimecrolimus in human whole blood by optimizing the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) preparation method. Whole blood was extracted into ethyl acetate, salted out with anhydrous magnesium sulfate, and purified with ethylenediamine-N-propyl silane adsorbent. The supernatant was evaporated under nitrogen until dry and finally reconstituted in methanol. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column in methanol (mobile phase A)-water (optimized for 0.1% acetic acid and 10 mM ammonium acetate, mobile phase B) at a 0.3 mL·min−1 flow rate. Electrospray ionization and positive ion multiple reaction monitoring were used for detection. The time for of analysis was 13 min. The calibration curves range of tacrolimus, rapamycin, everolimus and pimecrolimus were in the range of 1–100 ng·mL−1, mycophenolate mofetil in the range of 0.1–10 ng·mL−1 and mycophenolic acid at 10–1000 ng·mL−1. All correlation coefficients were >0.993. The coefficients of variation (CV, %) for inter-day and intra-day precision were less than 10%, while the spiked recoveries were in the range of 92.1% to 116%. Our method was rapid, sensitive, specific, and reproducible for the simultaneous determination of six immunosuppressants in human whole blood. Importantly, our approach can be used to monitor drug concentrations in the blood to facilitate disease treatment.

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Section: Comparisons With Other Methodsmentioning

confidence: 99%

Simultaneous Determination of Six Immunosuppressants in Human Whole Blood by HPLC-MS/MS Using a Modified QuEChERS Method

et al. 2022

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“…The HPLC instrument was a Portlab STAYER HPLC system equipped with a UV detector, parallel pump, and Triathlon autosampler (Portlab, Rome, Italy). The HPLC conditions were based on a published work with some modifications [70]: isocratic mode with acetonitrile/water (60:40, v/v), eluted at 0.8 mL/min, 15 µL injection volume, Zorbax C8, 4.6 mm ID × 250 mm, 5 µm column (Agilent, Milan, Italy) equilibrated at 55 • C. UV detection was performed at 278 nm. The RAD001 calibration curves were generated using dilutions of stock solutions, which were prepared as described above.…”

Section: Preparation Of Rad001-loaded Micellesmentioning

confidence: 99%

A Stable Micellar Formulation of RAD001 for Intracerebroventricular Delivery and the Treatment of Alzheimer’s Disease and Other Neurological Disorders

Gianessi,

Magini,

Dominici

et al. 2023

IJMS

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A large body of evidence, replicated in many mouse models of Alzheimer’s disease (AD), supports the therapeutic efficacy of the oral mammalian target of rapamycin inhibitors (mTOR-Is). Our preliminary data show that intracerebroventricular (ICV) administration of everolimus (RAD001) soon after clinical onset greatly diminished cognitive impairment and the intracellular beta amyloid and neurofibrillary tangle load. However, RAD001 shows >90% degradation after 7 days in solution at body temperature, thus hampering the development of proper therapeutic regimens for patients. To overcome such a drawback, we developed a stable, liquid formulation of mTOR-Is by loading RAD001 into distearoylphosphatidylethanolamine–polyethylene glycol 2000 (DSPE-PEG2000) micelles using the thin layer evaporation method. The formulation showed efficient encapsulation of RAD001 and a homogeneous colloidal size and stabilised RAD001, with over 95% of activity preserved after 14 days at 37 °C with a total decay only occurring after 98 days. RAD001-loaded DSPE-PEG2000 micelles were unchanged when stored at 4 and 25 °C over the time period investigated. The obtained formulation may represent a suitable platform for expedited clinical translation and effective therapeutic regimens in AD and other neurological diseases.

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“…[618][619][620][621][622] Under such conditions, concentrations in the order of ng mL −1 were detected. It can be noted that MS detection of mTOR inhibitors was mainly performed via adducts formation including sodium adducts 601,602 or ammonia adducts 623,624,625 because of the neutral character of these molecules. An LOQ often inferior to 1 ng mL −1 was obtained with MS detection.…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

Antineoplastic drugs and their analysis: a state of the art review

Guichard

Guillarme

Bonnabry

et al. 2017

Analyst

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The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

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Evaluation of a LC–MS method for everolimus preclinical determination in brain by using [13C2D4]RAD001 internal standard

Cited by 7 publications

References 22 publications

Simultaneous Determination of Six Immunosuppressants in Human Whole Blood by HPLC-MS/MS Using a Modified QuEChERS Method

Simultaneous Determination of Six Immunosuppressants in Human Whole Blood by HPLC-MS/MS Using a Modified QuEChERS Method

A Stable Micellar Formulation of RAD001 for Intracerebroventricular Delivery and the Treatment of Alzheimer’s Disease and Other Neurological Disorders

Antineoplastic drugs and their analysis: a state of the art review

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