Development and validation of an UHPLC-MS/MS method for simultaneous determination of palbociclib, letrozole and its metabolite carbinol in rat plasma and pharmacokinetic study application

Al‐Shehri, Mona M.; Hefnawy, Mohamed M.; Abuelizz, Hatem A.; Alzamil, Adeeba; Mohammed, Mostafa; Alsaif, Nawaf A.; Almehizia, Abdulrahman A.; Alkahtani, Hamad M.; Abounassif, Mohammad A.

doi:10.1016/j.arabjc.2019.05.005

Cited by 15 publications

(8 citation statements)

References 13 publications

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“…Providing an economically acceptable and still reliable bioanalytical method that could be implemented by financially burdened clinical facilities was one of the priorities of this study. A similar approach was adopted by Al-Shehri et al, who used paracetamol as IS in the LC-MS analysis of RIB, PAL and LET, or Shao et al, whose IS for LET was ANA [ 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

“…This is the first method which provides full chromatographic separation of all six analytes of interest; demonstrates the applicability of three detectors, including a diode array detector, a fluorescence detector and a QTOF MS detector; and is simple, selective and affordable. As opposed to previously published bioanalytical methods, that either did not include all analytes [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 37 ] or did not analyze all six drugs in real patient samples [ 13 ], we applied our method to analyze all the drugs of interest in real patients, in a clinical TDM context and for clinical pharmacokinetic evaluation.…”

Section: Resultsmentioning

confidence: 99%

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Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment

et al. 2022

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Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2− breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors’ peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between −1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between −14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2− breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment

et al. 2022

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“…The guidelines for bio-analytical method validation of the Food and Drug Administration (US-FDA) were followed for validation purposes [ 9 ]. Validation of the developed method in the rat plasma was carried out using specificity, sensitivity, linearity, precision, accuracy, extraction recovery, stability, dilution integrity, and matrix effect [ 14 , 15 , 16 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

A Liquid Chromatography Tandem Mass Spectrometry Method for the Simultaneous Estimation of the Dopamine Receptor Antagonist LE300 and Its N-methyl Metabolite in Plasma: Application to a Pharmacokinetic Study

et al. 2023

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LE300 is a novel dopamine receptor antagonist used to treat cocaine addiction. In the current study, a sensitive and fast liquid chromatography–tandem mass spectrometry (LC-MS/MS) has been established and validated for the simultaneous analysis of LE300 and its N-methyl metabolite, MLE300, in rat plasma with an application in a pharmacokinetic study. The chromatographic elution of LE300, MLE300, and Ponatinib (IS, internal standard), was carried out on a 50 mm C18 analytical column (ID: 2.1 mm and particle size: 1.8 μm) maintained at 22 ± 2 °C. The run time was 5 min at a flow rate of 0.3 mL/min. The mobile phase consisted of 42% aqueous solvent (10 mM ammonium formate, pH: 4.2 with formic acid) and 58% organic solvent (acetonitrile). Plasma samples were pretreated using protein precipitation with acetonitrile. The electrospray ionization (ESI) source was used to generate an ion-utilizing positive mode. A multiple reaction monitoring mass analyzer mode was utilized for the quantification of analytes. The linearity of the calibration curves in rat plasma ranged from 1 to 200 ng/mL (r2 = 0.9997) and from 2 to 200 ng/mL (r2 = 0.9984) for LE300 and MLE300, respectively. The lower limits of detection (LLOD) were 0.3 ng/mL and 0.7 ng/mL in rat plasma for LE300 and MLE300, respectively. Accuracy (RE%) ranged from −1.71% to −0.07% and −4.18% to −1.48% (inter-day), and from −3.3% to −1.47% and −4.89% to −2.15% (intra-day) for LE300 and MLE300, respectively. The precision (RSD%) was less than 2.43% and 1.77% for the inter-day, and 2.77% and 1.73% for intra-day of LE300 and MLE300, respectively. These results are in agreement with FDA guidelines. The developed LC-MS/MS method was applied in a pharmacokinetic study in Wistar rats. Tmax and Cmax were 2 h and 151.12 ± 12.5 ng/mL for LE300, and 3 h and 170.4 ± 23.3 ng/mL for MLE300.

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“…Few methods have been reported for the determination of PLB in pharmaceutical dosage forms and biological samples, mainly using UPLC, 5 HPLC, 6,7 and LC-MS/MS 8,9 methods. As far as we know, no spectrofluorimetric methods have yet been adopted for its determination.…”

Section: Introductionmentioning

confidence: 99%

Rapid microwave-assisted synthesis of nitrogen-doped carbon quantum dots as fluorescent nanosensors for the spectrofluorimetric determination of palbociclib: application for cellular imaging and selective probing in living cancer cells

2023

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Development and validation of an UHPLC-MS/MS method for simultaneous determination of palbociclib, letrozole and its metabolite carbinol in rat plasma and pharmacokinetic study application

Cited by 15 publications

References 13 publications

Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment

Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment

A Liquid Chromatography Tandem Mass Spectrometry Method for the Simultaneous Estimation of the Dopamine Receptor Antagonist LE300 and Its N-methyl Metabolite in Plasma: Application to a Pharmacokinetic Study

Rapid microwave-assisted synthesis of nitrogen-doped carbon quantum dots as fluorescent nanosensors for the spectrofluorimetric determination of palbociclib: application for cellular imaging and selective probing in living cancer cells

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