Validation of an LC–MS/MS method for simultaneous quantitation of enzalutamide, N -desmethylenzalutamide, apalutamide, darolutamide and ORM-15341 in mice plasma and its application to a mice pharmacokinetic study

Sulochana, Suresh P.; Saini, Neeraj Kumar; Daram, Prasanthi; Polina, Sai Babu; Mullangi, Ramesh

doi:10.1016/j.jpba.2018.04.038

Cited by 18 publications

(18 citation statements)

References 25 publications

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“…The terminal half‐life was 62.6 h. The clearance ( CL ) and volume of distribution were <1.0 mL/min/kg and 3.98 L/kg, respectively. The pharmacokinetics results of apalutamide in this study are in very close agreement with our earlier reported pharmacokinetic parameters determined using plasma as a matrix (Sulochana et al, ). This shows that DBS can be used as a promising alternative that is suitable for predicting exposure of apalutamide.…”

Section: Resultssupporting

confidence: 92%

“…Plasma was harvested from the blood samples collected from mice from group II by centrifuging the blood using a Biofuge (Hereaus, Germany) at 1760 g for 5 min and stored frozen (at −80 ± 10°C) until analysis. Plasma samples were analyzed by the method reported earlier (Sulochana et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Few LC–MS/MS methods have been reported for estimation of apalutamide alone (Hallur et al, ) or in combination with other drugs (Sulochana, Saini, Daram, Babu, & Mullangi, ). We have reported a validated LC–MS/MS method for the quantification of apalutamide in 50 μL mouse plasma with a lower limit of control (LLOQ) of 1.02 ng/mL.…”

Section: Introductionmentioning

confidence: 99%

“…Plasma samples were processed by simple protein precipitation and the chromatographic resolution was achieved on an Atlantis dC 18 column using an isocratic mobile with a total run time of 2.5 min (Hallur et al, ). Of late, Sulochana et al () have reported quantitation of apalutamide along with two other nonsteroidal anti‐androgens, namely enzalutamide and darolutamide and their active metabolites N ‐desmethylenzalutamide and ORM‐15341, respectively. Protein precipitation with acetonitrile was utilized for the extraction of these drugs and metabolites from mouse plasma.…”

Section: Introductionmentioning

confidence: 99%

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A novel dried blood spot LC–MS/MS method for the quantification of apalutamide in mouse whole blood: Application to pharmacokinetic study in mice

Saini

Sulochana

Kiran

et al. 2018

Biomedical Chromatography

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A simple, sensitive and rapid assay method has been developed and validated for the estimation of apalutamide on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The method utilizes liquid extraction of apalutamide from 3 mm punched disks from DBS cards (spiked or study samples). The extracted sample was chromatographed on an Atlantis dC column using gradient elution with 0.2% formic acid and acetonitrile at a flow rate of 1.00 mL/min. The total run time was 3.0 min. The MS/MS ion transitions monitored were m/z 478 → 450 for apalutamide and m/z 481 → 453 for the IS (apalutamide-d ). Method validation was performed as per regulatory guidelines. The assay was linear in the range of 0.95-2030 ng/mL. The intra- and inter-day precisions were in the ranges of 2.37-8.53 and 6.76-11.5%, respectively. Stability studies showed that apalutamide was stable on DBS cards for one month. This novel method has been applied to analyze the DBS samples of apalutamide obtained from a pharmacokinetic study in mice.

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Section: Resultssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel dried blood spot LC–MS/MS method for the quantification of apalutamide in mouse whole blood: Application to pharmacokinetic study in mice

Saini

Sulochana

Kiran

et al. 2018

Biomedical Chromatography

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“…We have also seen the similar trend in mice post-administration of darolutamide (▶Fig. 1c) orally and intravenously [17,18]. Currently Phase-3 clinical trials are being conducted with darolutamide (▶Fig.…”

Section: Introductionsupporting

confidence: 69%

RP-HPLC-UV Method for Simultaneous Quantification of Second Generation Non-Steroidal Antiandrogens Along with their Active Metabolites in Mice Plasma: Application to a Pharmacokinetic Study

et al. 2018

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A simple, specific and reproducible high-performance liquid chromatography (HPLC) assay method has been developed and validated for the quantitation of second generation antiandrogens and their active metabolites namely apalutamide, enzalutamide, N-desmethylenzalutamide (active metabolite of enzalutamide), darolutamide and ORM-15341 (active metabolite of darolutamide) in mice plasma. The method involves extraction of apalutamide, enzalutamide, N-desmethylenzalutamide, darolutamide and ORM-15341 along with internal standard (IS) from 100 µL mice plasma through a simple protein precipitation process. The chromatographic analysis was performed on a Waters Alliance HPLC system using a gradient mobile phase (comprising 10 mM ammonium acetate and acetonitrile in a flow-gradient) and X-Terra Phenyl column. The UV detection wave length was set at λmax 250 nm. Apalutamide, enzalutamide, N-desmethylenzalutamide, darolutamide and ORM-15341 and the IS eluted at 13.6, 11.4, 9.68, 6.11, 6.93 and 4.69 min, respectively with a total run time of 15 min. Method validation was performed as per regulatory guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 209 – 5215 ng/mL (r 2=0.998). The intra- and inter-day precisions were in the range of 0.56–13.5 and 1.04–13.9%, respectively. The validated HPLC method was successfully applied to a pharmacokinetic study in mice.

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Approved spectrofluorimetric strategies for assurance of three modern antineoplastic drugs: tepotinib, sotorasib, and darolutamide in their dose forms and biological liquids utilizing mercurochrome

et al. 2022

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An approved, straightforward, fast, and delicate spectrofluorimetric strategy was developed for the estimation of tepotinib (TEPO), sotorasib (SOTO), and darolutamide (DARO) as new antineoplastic drugs. The spectrofluorimetric strategy was based on quantitative fluorescence quenching of MER at 538 nm after being excited at 350 nm by the addition of the cited drugs in the presence of acetate buffer (pH 3.5). The degree of fluorescence quenching was directly proportional to the concentrations of the cited drugs within the concentration range of 0.5-10.0, 0.2-10, and 0.4-10.0 μg ml À1 for TEPO, SOTO, and DARO, respectively. Mean ± standard deviation (SD) were calculated for the studied drugs as follows; 99.9 ± 0.87, 99.72 ± 1.08, and 100.21 ± 1.44, for TEPO, SOTO, and DARO, respectively. Limit of detection (LOD) values were 0.16, 0.05, and 0.11 μg ml À1 , whereas limit of quantitation (LOQ) values were 0.5, 0.15, and 0.36 μg ml À1 for TEPO, SOTO, and DARO, respectively. Statistical comparison through detailed strategies produced greater understanding and found that there were no noteworthy contrasts in exactness and exactness between strategies. The proposed strategy was used effectively to analyze the measurement of different forms of the examined drugs. Moreover, the recommended fluorimetric strategy was used for examination of TEPO, SOTO, and DARO in human plasma and urine tests.

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Validation of an LC–MS/MS method for simultaneous quantitation of enzalutamide, N -desmethylenzalutamide, apalutamide, darolutamide and ORM-15341 in mice plasma and its application to a mice pharmacokinetic study

Cited by 18 publications

References 25 publications

A novel dried blood spot LC–MS/MS method for the quantification of apalutamide in mouse whole blood: Application to pharmacokinetic study in mice

A novel dried blood spot LC–MS/MS method for the quantification of apalutamide in mouse whole blood: Application to pharmacokinetic study in mice

RP-HPLC-UV Method for Simultaneous Quantification of Second Generation Non-Steroidal Antiandrogens Along with their Active Metabolites in Mice Plasma: Application to a Pharmacokinetic Study

Approved spectrofluorimetric strategies for assurance of three modern antineoplastic drugs: tepotinib, sotorasib, and darolutamide in their dose forms and biological liquids utilizing mercurochrome

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