scholarly journals Development and validation of a novel method for simultaneous quantification of enzalutamide, darolutamide and their active metabolites in mice dried blood spots using LC-MS/MS: Application to pharmacokinetic study in mice

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 242-257 ◽  
Author(s):  
Neeraj Kumar Saini ◽  
Suresh P Sulochana ◽  
Mohd Zainuddin ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Active Metabolite ◽  
Dried Blood Spots ◽  
Assay Method ◽  
Active Metabolites ◽  
Blood Spots ◽  
Accuracy And Precision ◽  
Novel Method ◽  
Development And Validation ◽  
Regulatory Guideline

A simple, sensitive and rapid assay method has been developed and validated for the estimation of enzalutamide, N-desmethylenzalutamide (active metabolite of enzalutamide), darolutamide and ORM-15341 (active metabolite of darolutamide) on mice dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electro spray ionization in the positive-ion mode. The method utilizes liquid extraction of enzalutamide, N-desmethylenzalutamide, darolutamide and ORM-15341 from 3 mm punched disks from DBS cards (spiked or study samples). The extracted sample was chromatographed using an isocratic mobile phase (0.2 % formic acid : acetonitrile; 30:70, v/v) on an Atlantis dC18 column. The total run time was 2.5 min. The MS/MS ion transitions monitored were m/z 465 → m/z 209, m/z 451 →  m/z 195, m/z 399 → m/z 178, m/z 397 →  m/z 194 and m/z 481 → m/z 453 for enzalutamide, N-desmethyl­enzalutamide, darolutamide, ORM-15341 and the IS (apalutamide-d3), respectively. Method validation was performed as per regulatory guideline. The assay had a good linearity over the range of 0.93-2000 ng/mL. The intra- and inter-batch accuracy and precision (%RE & RSD) across quality controls met the acceptance criteria for all the analytes. Stability studies showed that all the analytes were stable on DBS cards for one month. This novel method has been applied to analyze the DBS samples of enzalutamide, N-desmethylenzalutamide, darolutamide and ORM-15341 obtained from a pharmacokinetic study in mice.

Determination of Tofacitinib in Mice Whole Blood on Dried Blood Spots Using LC–ESI–MS/MS: Application to Pharmacokinetic Study in Mice

Drug Research ◽  
2018 ◽  
Vol 69 (06) ◽  
pp. 330-336 ◽  
Author(s):  
Abhishek Dixit ◽  
Sadanand Rangnathrao Mallurwar ◽  
Suresh P Sulochana ◽  
Mohd Zainuddin ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Whole Blood ◽  
Internal Standard ◽  
Dried Blood Spots ◽  
Assay Method ◽  
Blood Spots ◽  
Novel Method ◽  
Positive Ion ◽  
Regulatory Guideline

AbstractA simple, sensitive and rapid assay method has been developed and validated as per regulatory guideline for the estimation of tofacitinib on mice dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electro spray ionization in the positive-ion mode. The method employs liquid extraction of tofacitinib from DBS disk of mice whole blood followed by chromatographic separation using 5 mM ammonium acetate (pH 6.5):acetonitrile (20:80, v/v) at a flow rate of 0.60 mL/min on an X-Terra Phenyl column with a total run time 2.5 min. The MS/MS ion transitions monitored were m/z 313→149 for tofacitinib and m/z 316→149 for the internal standard (13C3, 15N-tofacitinib). The assay was linear in the range of 0.99–1980 ng/mL. The intra- and inter-day precision was in the range of 1.17–10.3 and 3.37–10.9%, respectively. Stability studies showed that tofacitinib was stable on DBS cards for one month. This novel method has been applied to analyze the DBS samples of tofacitinib obtained from a pharmacokinetic study in mice.

scholarly journals Development and validation of a LC-MS/MS method for ivermectin quantification in dried blood spots: application to a pharmacokinetic study inTrichuris trichiura-infected adults

2018 ◽  
Vol 10 (24) ◽  
pp. 2901-2909 ◽  
Author(s):  
Jessica D. Schulz ◽  
Anna Neodo ◽  
Jean T. Coulibaly ◽  
Jennifer Keiser
Keyword(s):  
Pharmacokinetic Study ◽  
Dried Blood Spots ◽  
Trichuris Trichiura ◽  
Dried Blood Spot ◽  
Plasma Samples ◽  
Blood Spots ◽  
Development And Validation ◽  
Blood Spot

Ivermectin was quantified in dried blood spot and plasma samples derived fromTrichuris trichiura-infected adults with a validated LC-MS/MS method.

scholarly journals 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

Drug Research ◽  
2018 ◽  
Vol 69 (10) ◽  
pp. 537-544
Author(s):  
Ashok Zakkula ◽  
Vinay Kiran ◽  
Umesh Todmal ◽  
Suresh P Sulochana ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Active Metabolite ◽  
High Performance ◽  
Second Generation ◽  
Wave Length ◽  
Internal Standard ◽  
Hplc Method ◽  
Assay Method ◽  
Precipitation Process ◽  
Active Metabolites

AbstractA 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.

scholarly journals Simplified and Rapid Determination of Primaquine and 5,6-Orthoquinone Primaquine by UHPLC-MS/MS: Its Application to a Pharmacokinetic Study

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4357
Author(s):  
Waritda Pookmanee ◽  
Siriwan Thongthip ◽  
Jeeranut Tankanitlert ◽  
Mathirut Mungthin ◽  
Chonlaphat Sukasem ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
High Performance ◽  
Rapid Determination ◽  
Active Metabolites ◽  
Chromatography Tandem Mass Spectrometry ◽  
Accuracy And Precision ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Isocratic Mode

The method for the determination of primaquine (PQ) and 5,6-orthoquinone primaquine (5,6-PQ), the representative marker for PQ active metabolites, via CYP2D6 in human plasma and urine has been validated. All samples were extracted using acetonitrile for protein precipitation and analyzed using the ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) system. Chromatography separation was carried out using a Hypersil GOLDTM aQ C18 column (100 × 2.1 mm, particle size 1.9 μm) with a C18 guard column (4 × 3 mm) flowed with an isocratic mode of methanol, water, and acetonitrile in an optimal ratio at 0.4 mL/min. The retention times of 5,6-PQ and PQ in plasma and urine were 0.8 and 1.6 min, respectively. The method was validated according to the guideline. The linearity of the analytes was in the range of 25–1500 ng/mL. The matrix effect of PQ and 5,6-PQ ranged from 100% to 116% and from 87% to 104% for plasma, and from 87% to 89% and from 86% to 87% for urine, respectively. The recovery of PQ and 5,6-PQ ranged from 78% to 95% and form 80% to 98% for plasma, and from 102% to from 112% to 97% to 109% for urine, respectively. The accuracy and precision of PQ and 5,6-PQ in plasma and urine were within the acceptance criteria. The samples should be kept in the freezer (−80 °C) and analyzed within 7 days due to the metabolite stability. This validated UHPLC-MS/MS method was beneficial for a pharmacokinetic study in subjects receiving PQ.

scholarly journals Development and validation of an analytical method using UPLC–MS/MS to quantify everolimus in dried blood spots in the oncology setting

2018 ◽  
Vol 149 ◽  
pp. 106-113 ◽  
Author(s):  
Lotte M. Knapen ◽  
Yvo de Beer ◽  
Roger J.M. Brüggemann ◽  
Leo M. Stolk ◽  
Frank de Vries ◽  
...  
Keyword(s):  
Analytical Method ◽  
Dried Blood Spots ◽  
Blood Spots ◽  
Development And Validation

scholarly journals A ‘Dilute and Shoot’ Liquid Chromatography-Mass Spectrometry Method for Multiclass Drug Analysis in Pre-Cut Dried Blood Spots

2021 ◽  
Vol 18 (6) ◽  
pp. 3068
Author(s):  
Lucia Mainero Rocca ◽  
Nunziata L’Episcopo ◽  
Andrea Gordiani ◽  
Matteo Vitali ◽  
Alessandro Staderini
Keyword(s):  
Whole Blood ◽  
Occupational Safety ◽  
Method Development ◽  
Beta Blockers ◽  
Dried Blood Spots ◽  
Drug Analysis ◽  
Triple Quadrupole Mass Spectrometer ◽  
Blood Spots ◽  
Accuracy And Precision ◽  
Study Results

Drugs able to affect the auditory and nervous systems and consumed by workers to treatdifferent pathologies can represent a possible source of risk in the work environment. All the target compounds involved in the presented project show ototoxic and/or narcoleptic side effects and, for these reasons, occupational safety organizations have recognized them as potential causes of work injuries. A multiclass method for the analysis of 15 drugs among the most widespread worldwide (belonging to nine different classes including antihistamines, beta-blockers, antidepressants, Z-drugs and opioids), was developed and validated. This study describes a rapid, sensitive and effective method to analyse these substances in whole blood using tailored pre-cut dried blood spots. Detection was achieved with a triple quadrupole mass spectrometer after an easy and simple ‘dilute and shoot’ solubilisation followed by an UPLC separation. All the issues linked to the use of the dried blood spots and whole blood, such as haematocrit variability, volumetric evaluation and sample carrier choice were carefully studied and managed during method development. From the validation study results it emerged that this approach can be deemed successful thanks to its few pg µL−1 LOQs, good linear intervals, absolute recoveries of no less than 75%, an almost negligible matrix effect and accuracy and precision in line with the European and American guidelines for validation. All the obtained goals have been specifically pursued in order to encourage method diffusion as a primary prevention intervention, even in small private workplaces.

Quantitation of Ivosidenib, A Novel Mutant IDH1 Inhibitoron Mice DBS: Application to a Pharmacokinetic Study

Drug Research ◽  
2019 ◽  
Vol 69 (09) ◽  
pp. 505-511 ◽  
Author(s):  
Sreekanth Dittakavi ◽  
Rakesh Kumar Jat ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Plasma Concentrations ◽  
Internal Standard ◽  
Dried Blood Spots ◽  
Pharmacokinetic Analysis ◽  
Validation Parameters ◽  
Chromatographic Resolution ◽  
Mutant Idh1 ◽  
Intravenous And Oral Administration ◽  
Regulatory Guideline

AbstractIvosidenib is an approved drug for relapsed or refractory IDH1 mutant AML patients. The goal of the present work is to develop and validate an LC-MS/MS method for the quantitation of ivosidenib in mice dried blood spots (DBS) as per regulatory guideline in the linearity range of 1.10–3293 ng/mL. To date there is no bioanalytical method reported for quantitation of ivosidenib. The chromatographic resolution of ivosidenib and internal standard (warfarin) was achieved on a C18 column with an isocratic mobile phase. All validation parameters met the acceptance criteria. The intra- and inter-day precision was in the range of 2.79–10.5 and 5.76–9.02%, respectively. Ivosidenib was stable for 3 freeze/thaw cycles, up to 7 days at room temperature and for one month at −80°C. The applicability of the validated method is shown in a mice pharmacokinetic study. Ivosidenib was quantifiable up to 24 and 36 h following intravenous and oral administration to mice, respectively. The oral bioavailability was 48%. Comparison of DBS vs. plasma concentrations of ivosidenib showed excellent correlation, indicating DBS can be used as an alternative for plasma for pharmacokinetic analysis.

Validated HPLC Method for Quantification of a Novel Trk Inhibitor, Larotrectinib in Mice Plasma: Application to a Pharmacokinetic Study

Drug Research ◽  
2020 ◽  
Vol 70 (02/03) ◽  
pp. 101-106
Author(s):  
Harsha K. Tripathy ◽  
S.V. Nair Manju ◽  
Ashok Zakkula ◽  
Ram Murthi Bestha ◽  
Sreekanth Dittakavi ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
High Performance ◽  
Wave Length ◽  
Internal Standard ◽  
Hplc Method ◽  
Long Term Storage ◽  
Development And Validation ◽  
Orally Active ◽  
Regulatory Guideline

AbstractLarotrectinib, is an orally active novel small molecule approved for the treatment of solid tumors in pediatrics and adult patients. It acts by inhibiting tropomyosin receptor kinase. In this paper, we report the development and validation of a high-performance liquid chromatography (HPLC) method for the quantitation of larotrectinib in mice plasma as per the FDA regulatory guideline. Plasma samples processing was accomplished through simple protein precipitation using acetonitrile enriched with internal standard (IS, enasidenib). The chromatographic analysis was performed using a gradient mobile phase comprising 10 mM ammonium acetate and acetonitrile at a flow-rate of 0.8 mL/min on an X-Terra Phenyl column. The UV detection wave length was set at λmax 262 nm. Larotrectinib and the IS eluted at 3.85 and 6.60 min, respectively with a total run time of 8.0 min. The calibration curve was linear over a concentration range of 0.20–5.00 μg/mL (r2=≥0.992). The intra- and inter-day precision and accuracy results were within the acceptable limits. Results of stability studies indicated that larotrectinib was stable on bench-top, in auto-sampler, up to three freeze/thaw cycles and long-term storage at −80°C. The validated HPLC method was successfully applied to a pharmacokinetic study in mice.

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