SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women
A rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE) of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on A...
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doaj-e262885f7dae473c898f1bf3633a84842021-04-02T04:36:27ZengElsevierJournal of Pharmaceutical Analysis2095-17792016-08-016427628110.1016/j.jpha.2016.05.004SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian womenPravin G. Vanol0Puran Singhal1Priyanka A. Shah2Jaivik V. Shah3Pranav S. Shrivastav4Mallika Sanyal5Chemistry Department, St. Xavier's College, Navrangpura, Ahmedabad 380009, IndiaBioanalytical Department, Alkem Laboratories Ltd., Lower Parel, Mumbai 400013, IndiaDepartment of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, IndiaDepartment of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, IndiaDepartment of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, IndiaChemistry Department, St. Xavier's College, Navrangpura, Ahmedabad 380009, IndiaA rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE) of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on Acquity UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm) column using methanol-0.1% formic acid in water (85:15, v/v) as the mobile phase. Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM) following the transitions at m/z 286.2→217.0 and m/z 290.2→221.0, respectively. The calibration plots were linear through the concentration range of 0.10–100 ng/mL (r2≥0.9990) using 100 µL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was ≤5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR) of 74 subject samples.http://www.sciencedirect.com/science/article/pii/S2095177916300508LetrozoleLetrozole-D4UPLC–MS/MSSolid phase extractionBioequivalence study |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pravin G. Vanol Puran Singhal Priyanka A. Shah Jaivik V. Shah Pranav S. Shrivastav Mallika Sanyal |
spellingShingle |
Pravin G. Vanol Puran Singhal Priyanka A. Shah Jaivik V. Shah Pranav S. Shrivastav Mallika Sanyal SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women Journal of Pharmaceutical Analysis Letrozole Letrozole-D4 UPLC–MS/MS Solid phase extraction Bioequivalence study |
author_facet |
Pravin G. Vanol Puran Singhal Priyanka A. Shah Jaivik V. Shah Pranav S. Shrivastav Mallika Sanyal |
author_sort |
Pravin G. Vanol |
title |
SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women |
title_short |
SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women |
title_full |
SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women |
title_fullStr |
SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women |
title_full_unstemmed |
SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women |
title_sort |
spe–uplc–ms/ms assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal indian women |
publisher |
Elsevier |
series |
Journal of Pharmaceutical Analysis |
issn |
2095-1779 |
publishDate |
2016-08-01 |
description |
A rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE) of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on Acquity UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm) column using methanol-0.1% formic acid in water (85:15, v/v) as the mobile phase. Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM) following the transitions at m/z 286.2→217.0 and m/z 290.2→221.0, respectively. The calibration plots were linear through the concentration range of 0.10–100 ng/mL (r2≥0.9990) using 100 µL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was ≤5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR) of 74 subject samples. |
topic |
Letrozole Letrozole-D4 UPLC–MS/MS Solid phase extraction Bioequivalence study |
url |
http://www.sciencedirect.com/science/article/pii/S2095177916300508 |
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