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 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.

scholarly journals Validated LC-ESI-MS/MS method for the determination of ivosidenib in 10 µL mice plasma: application to a pharmacokinetic study

ADMET & DMPK ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 131-139 ◽  
Author(s):  
Sreekanth Dittakavi ◽  
Rakesh Kumar Jat ◽  
Sadanand Rangnathrao Mallurwar ◽  
Ravi Kumar Jairam ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Precipitation Process ◽  
Esi Ms ◽  
Accuracy And Precision ◽  
Multiple Reaction Monitoring Mode ◽  
Positive Ion ◽  
Regulatory Guideline

A simple, selective and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of ivosidenib in mice plasma using warfarin as an internal standard (I.S.) as per regulatory guideline. Sample preparation was accomplished through a simple protein precipitation process. Chromatography of ivosidenib and the I.S. was achieved on an Atlantis dC18 column using an isocratic mobile phase comprising 0.2 % formic acid in water and acetonitrile (25:75, v/v) delivered at a flow rate of 1.0 mL/min. LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique in positive ion mode and the transitions of m/z 583.1→186.1 and m/z 309.2→251.3 were used to quantitate ivosidenib and the I.S, respectively. The total chromatographic run time was 2.0 min. Linearity was established in the concentration range of 1.10-3293 ng/mL (r2>0.99). The intra- and inter-day accuracy and precision for ivosidenib in mice plasma were in the range of 5.72-9.91 and 5.90-10.7 %, respectively. Ivosidenib was found to be stable on bench-top for 6 h, up to three freeze-thaw cycles, in in-injector for 24 h and for one month at -80 °C. The applicability of the validated method has been demonstrated in a mice pharmacokinetic study. Following intravenous (2 mg/kg) and oral (5 mg/kg) administration of ivosidenib to mice, concentrations were quantifiable up to 24 and 48 h, respectively. The bioavailability was 61 %.

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.

scholarly journals LC–HRMS determination of piperine on rat dried blood spots: A pharmacokinetic study

2016 ◽  
Vol 6 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Bokka Ramesh ◽  
P. Rajesh Rao Vadaparthi ◽  
Genji Sukumar ◽  
Nemali Manjula ◽  
Katragadda Suresh Babu ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Dried Blood Spots ◽  
Blood Spots

Development of an LC-MS/MS method for determination of bicalutamide on dried blood spots: application to pharmacokinetic study in mice

2014 ◽  
Vol 29 (2) ◽  
pp. 254-260 ◽  
Author(s):  
Suresh P. S. ◽  
S. Vijay Kumar ◽  
Avinash Kumar ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Dried Blood Spots ◽  
Blood Spots

Sensitive LC-MS/MS Method for the Simultaneous Determination of Bendamustine and its Active Metabolite, γ-Hydroxybendamustine in Small Volume Mice and Dog Plasma and its Application to a Pharmacokinetic Study in Mice and Dogs

Drug Research ◽  
2017 ◽  
Vol 67 (09) ◽  
pp. 497-508 ◽  
Author(s):  
Devaraj Chandrashekar ◽  
Ponnayyan Suresh ◽  
Rajnish Kumar ◽  
Ravi Bhamidipati ◽  
Ramesh Mullangi ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Small Volume ◽  
Internal Standard ◽  
Simultaneous Quantification ◽  
Liquid Liquid Extraction ◽  
Dog Plasma ◽  
Highly Sensitive ◽  
Regulatory Guidelines ◽  
Novel Method

AbstractA highly sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the simultaneous quantification of bendamustine (BM) and γ-hydroxybendamustine (HBM) in small volume (20 µL) mice and dog plasma using phenacetin as an internal standard (IS) as per regulatory guidelines. Both the analytes and IS were extracted from mice and dog plasma using a liquid-liquid extraction method. Chromatography was achieved on Atlantis dC18 column using an isocratic mobile phase (0.2% formic acid:acetonitrile, 25:75) at a flow rate of 0.40 mL/min. The total chromatographic run time was 3.0 min and the elution of BM, HBM and IS occurred at ~1.2, 1.2 and 2.0 min, respectively. A linear response function was established 0.11–518 ng/mL for both the analytes in mice and dog plasma. The intra- and inter-day accuracy and precisions were in the range of 3.46–12.9 and 3.63–8.23%; 1.15–9.00 and 7.86–9.49% for BM and HBM, respectively in mice plasma and 2.15–6.49 and 1.73–13.1%; 4.35–13.9 and 4.33–10.5% for BM and HBM, respectively in dog plasma. This novel method has been applied to a pharmacokinetic study in mice and dogs.

scholarly journals DEVELOPMENT OF REAL-TIME MULTIPLEX PCR FOR THE QUANTITATIVE DETERMINATION OF TREC'S AND KREC'S IN WHOLE BLOOD AND IN DRIED BLOOD SPOTS

2015 ◽  
Vol 17 (5) ◽  
pp. 467 ◽  
Author(s):  
M. A. Gordukova ◽  
I. P. Oskorbin ◽  
O. V. Mishukova ◽  
S. B. Zimin ◽  
N. V. Zinovieva ◽  
...  
Keyword(s):  
Quantitative Determination ◽  
Multiplex Pcr ◽  
Real Time ◽  
Whole Blood ◽  
Dried Blood Spots ◽  
Blood Spots

LC–MS/MS determination of pramipexole on rat dried blood spots: A pharmacokinetic study

2013 ◽  
Vol 932 ◽  
pp. 34-39 ◽  
Author(s):  
R. Nageswara Rao ◽  
B. Sravan ◽  
K. Ramakrishna ◽  
B. Raju ◽  
R. Srinivas
Keyword(s):  
Pharmacokinetic Study ◽  
Dried Blood Spots ◽  
Blood Spots

scholarly journals Tandem Mass Spectrometry for the Direct Assay of Enzymes in Dried Blood Spots: Application to Newborn Screening for Mucopolysaccharidosis II (Hunter Disease)

2007 ◽  
Vol 53 (1) ◽  
pp. 137-140 ◽  
Author(s):  
Ding Wang ◽  
Tim Wood ◽  
Martin Sadilek ◽  
C Ronald Scott ◽  
Frantisek Turecek ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Internal Standard ◽  
Hunter Syndrome ◽  
Dried Blood Spots ◽  
Assay Method ◽  
Tandem Mass ◽  
Mucopolysaccharidosis Ii ◽  
Blood Spots

Abstract Background: A treatment for mucopolysaccharidosis II (Hunter syndrome) has recently become available. Therefore, we developed a high-throughput assay method appropriate for newborn screening for the relevant enzyme, iduronate 2-sulfatase. Methods: We synthesized a new iduronate 2-sulfatase substrate that can be used to assay the enzyme by use of tandem mass spectrometry together with an internal standard. The assay uses a dried blood spot on a newborn screening card as the enzyme source. Results: When the assay was tested on dried blood spots, the iduronate 2-sulfatase activity measured for 13 patients with Hunter syndrome was well below the interval found for 57 randomly chosen newborns. The assay was more sensitive than previously reported iduronate 2-sulfatase assays. Conclusions: This newly developed tandem mass spectrometry assay has the potential to be adopted for newborn screening of Hunter syndrome. This method also has the potential to be carried out in multiplex fashion to assay several different enzymes relevant to lysosomal storage diseases that are assayed in a single infusion into the mass spectrometer.

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