Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Mass spectrometric conditions for cyclobenzaprine, desmethyl cyclobenzaprine and cyclobenzaprine N-oxide. ESI: electrospray ionization, m/z: mass-to-charge ratio, msec: millisecond.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: LC-MS/MS chromatogram of desmethyl cyclobenzaprine, cyclobenzaprine, cyclobenzaprine-d3 and cyclobenzaprine N-oxide with the respective structural formula.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Liquid Chromatography with Mass Spectroscopy

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Summary of accuracy and precision results for cyclobenzaprine, desmethyl cyclobenzaprine and cyclobenzaprine N-oxide (accuracy presented as mean relative error and precision as coefficient of variation, n = 5 per run). CV, coefficient of variation; LLOQ, Lower limit of quantification; QC, quality control.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Control

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Impact of excipient addition in preformulation and formulation development of cyclobenzaprine. A : Cumulative amount of permeated drug per cm 2 of the respective sublingual tablet (mean ± SEM; n ≥ 5). B : Cumulative amount of permeated drug per cm 2 of the respective solution (mean ± SEM; n ≥ 5) adapted from , Int. J. Pharm. 2021. C : Dissolution of the respective sublingual tablet (mean ± SEM; n = 3). D : Correlation of obtained cyclobenzaprine permeability with the added amount of dibasic phosphate (mean ± SEM). R 2 : determination coefficient, SEM: standard error of the mean, *: significant value (p < 0.05; unpaired t-test).

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Formulation, Dissolution, Permeability

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Disintegration of cyclobenzaprine sublingual tablets after addition of 150 µL freshly collected human saliva in dependence on time.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Cytochrome P450 metabolism of cyclobenzaprine. A : Scheme of cyclobenzaprine demethylation by CYP isoenzymes. B : Cumulative amount of permeated desmethyl cyclobenzaprine per cm 2 (mean ± SEM; n = 8). C : Formation of desmethyl cyclobenzaprine by different mucosae and approaches (mean ± SEM; n ≥ 2). D : Formation of desmethyl cyclobenzaprine by human liver microsomes per time (mean ± SEM; n = 3). HLM: human liver microsomes, LLOQ: lower limit of quantification .

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Alteration of cyclobenzaprine sublingual tablets under ambient and stress conditions. ( A ): Cumulative amount of permeated drug per cm 2 of the respective sublingual tablet stored (mean ± SEM; n ≥ 4). ( B ): Dissolution of the respective sublingual tablet stored (mean ± SEM; n = 3). ( C , D ): Visual and microscopic inspection of the primary packaging material and the tablet surface after storage under ambient conditions and stress conditions, respectively. ( E , F ): TOF-MS scan of the rinsed residuals from packaging material after storage under ambient conditions and stress conditions, respectively. m/z: mass-to-charge ratio, SEM: standard error of the mean , *: significant value (p < 0.05; unpaired t-test).

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Dissolution

Journal: eLife

Article Title: An NKX2-1/ERK/WNT feedback loop modulates gastric identity and response to targeted therapy in lung adenocarcinoma

doi: 10.7554/elife.66788

Figure Lengend Snippet: Figure 4. NKX2-1 status modulates response to MAPK pathway inhibitors. (A) Representative H and E and phospho-ERK1/2 immunostaining photomicrographs of paraffin-embedded lung sections from BrafLSL-V600E/+;Trp53f/f;Nkx2-1f/+;Rosa26LSL-tdTomato/LSL-tdTomato and BrafLSL-V600E/+;Trp53f/f; Nkx2-1f/f;Rosa26LSL-tdTomato/LSL-tdTomato mice that were treated with control chow (BP C/BPN C) or chow containing PLX4720 (200 mg/kg) and PD0325901 (7 mg/kg) inhibitors (BP Tx/BPN Tx) for 2 weeks starting at 6 weeks post-tumor initiation with PGK-Cre lentivirus (5 103 pfu/mouse). Scale bar: 100 mm. Figure 4 continued on next page

Article Snippet: DOI: https://doi.org/10.7554/eLife.66788 25 of 42 Continued Reagent type (species) or resource Designation Source or reference Identifiers Additional information Genetic reagent (Mus musculus) KrasLSL-G12D/+ Jackson et al., 2001 PMID:11751630 MGI:2429948 Dr. Tyler Jacks (MIT, Cambridge, Massachusetts); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) KrasFSF-G12D/+ Young et al., 2011 PMID:21512139 MGI:5007794 Dr. Tyler Jacks (MIT, Cambridge, Massachusetts); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Nkx2-1f/f Kusakabe et al., 2006 PMID:16601074 MGI: 3653706 Dr. Shioko Kimura (NCI, NIH, Bethseda, Maryland); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Rosa26LSL-tdTomato Ai14 Madisen et al., 2010 PMID:20023653 MGI: 4436847 Jackson Laboratories (Bar Harbor, Maine); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Rosa26FSF-CreERT2 Schönhuber et al., 2014 PMID:25326799 MGI: 5616874 Dr. Dieter Saur (Technische Universitat Munchen, Munchen, Germany); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Foxa1f/f Gao et al., 2008 PMID:19141476 MGI: 3831163 Dr. Klaus H. Kaestner (Univ. of Pennsylvania School of Medicine, Philadelphia, PA); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Foxa2f/f Sund et al., 2000 PMID:10866673 MGI: 2177357 Dr. Klaus H. Kaestner (Univ. of Pennsylvania School of Medicine, Philadelphia, PA); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) NOD/SCID-gamma chain deficient (NSG) The Jackson Laboratory 005557 Cell line (Homo sapiens) 293T DuPage et al., 2009 PMID:19561589 Cell line (Mus musculus) L-WRN ATCC CRL-3276 Recombinant DNA reagent d8.9 (plasmid) DuPage et al., 2009 PMID:19561589 Recombinant DNA reagent VSV-G (plasmid) DuPage et al., 2009 PMID:19561589 Recombinant DNA reagent 7TGP (plasmid) Addgene 24305 Chemical compound, drug Tamoxifen Sigma Aldrich T5648 Chemical compound, drug Tamoxifen supplemented chow Envigo TD.130858 Chemical compound, drug PLX4720 supplemented chow Plexxikon/ Research Diets Tsai et al., 2008 Chemical compound, drug PD0325901 supplemented chow Plexxikon/ Research Diets Trejo et al., 2012 Chemical compound, drug PLX4720 Selleckchem S1152 Chemical compound, drug PD0325901 Selleckchem S1036 Chemical compound, drug GDC-0994 Genentech Blake et al., 2016 Continued on next page Zewdu et al. eLife 2021;10:e66788.

Techniques: Immunostaining, Control

Journal: eLife

Article Title: An NKX2-1/ERK/WNT feedback loop modulates gastric identity and response to targeted therapy in lung adenocarcinoma

doi: 10.7554/elife.66788

Figure Lengend Snippet: Figure 7. MAPK inhibition activates WNT signaling in NKX2-1-negative tumors. (A) Transcriptome analysis of genes comprising the canonical WNT pathway gene ontology (AmiGO) in RNA purified from FACS-sorted BPN tumor cells 1 week post- treatment with PLX4720+PD0325901 or control chow. adjP <0.05 for each comparison. Color key indicates normalized expression levels (Log10). (B) Analysis of WNT pathway activity in scRNA-seq data using a WNT activation signature. BP indicates cells from clusters 4–8; BPN indicates cells from clusters 1–3 (see Figure 4E, F). C : control, Tx = drug Figure 7 continued on next page

Article Snippet: DOI: https://doi.org/10.7554/eLife.66788 25 of 42 Continued Reagent type (species) or resource Designation Source or reference Identifiers Additional information Genetic reagent (Mus musculus) KrasLSL-G12D/+ Jackson et al., 2001 PMID:11751630 MGI:2429948 Dr. Tyler Jacks (MIT, Cambridge, Massachusetts); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) KrasFSF-G12D/+ Young et al., 2011 PMID:21512139 MGI:5007794 Dr. Tyler Jacks (MIT, Cambridge, Massachusetts); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Nkx2-1f/f Kusakabe et al., 2006 PMID:16601074 MGI: 3653706 Dr. Shioko Kimura (NCI, NIH, Bethseda, Maryland); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Rosa26LSL-tdTomato Ai14 Madisen et al., 2010 PMID:20023653 MGI: 4436847 Jackson Laboratories (Bar Harbor, Maine); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Rosa26FSF-CreERT2 Schönhuber et al., 2014 PMID:25326799 MGI: 5616874 Dr. Dieter Saur (Technische Universitat Munchen, Munchen, Germany); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Foxa1f/f Gao et al., 2008 PMID:19141476 MGI: 3831163 Dr. Klaus H. Kaestner (Univ. of Pennsylvania School of Medicine, Philadelphia, PA); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) Foxa2f/f Sund et al., 2000 PMID:10866673 MGI: 2177357 Dr. Klaus H. Kaestner (Univ. of Pennsylvania School of Medicine, Philadelphia, PA); mixed C57BL/6J 129SvJ background Genetic reagent (Mus musculus) NOD/SCID-gamma chain deficient (NSG) The Jackson Laboratory 005557 Cell line (Homo sapiens) 293T DuPage et al., 2009 PMID:19561589 Cell line (Mus musculus) L-WRN ATCC CRL-3276 Recombinant DNA reagent d8.9 (plasmid) DuPage et al., 2009 PMID:19561589 Recombinant DNA reagent VSV-G (plasmid) DuPage et al., 2009 PMID:19561589 Recombinant DNA reagent 7TGP (plasmid) Addgene 24305 Chemical compound, drug Tamoxifen Sigma Aldrich T5648 Chemical compound, drug Tamoxifen supplemented chow Envigo TD.130858 Chemical compound, drug PLX4720 supplemented chow Plexxikon/ Research Diets Tsai et al., 2008 Chemical compound, drug PD0325901 supplemented chow Plexxikon/ Research Diets Trejo et al., 2012 Chemical compound, drug PLX4720 Selleckchem S1152 Chemical compound, drug PD0325901 Selleckchem S1036 Chemical compound, drug GDC-0994 Genentech Blake et al., 2016 Continued on next page Zewdu et al. eLife 2021;10:e66788.

Techniques: Inhibition, Purification, Control, Comparison, Expressing, Activity Assay, Activation Assay

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Mean plasma pantoprazole concentration (logarithmic scale) vs. time (hr) profiles for neonatal calves ( n = 9) following intravenous (IV) single dose administration of 1.0 mg/kg of pantoprazole.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Pantoprazole pharmacokinetic parameters following a single intravenous (1 mg/kg) administration to neonatal Holstein calves.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques:

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Tissue concentrations of pantoprazole sulfone (μg/g) in collected tissues 1, 3, and 5 days after intravenous administration of pantoprazole (1 mg/kg) from study calves.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques:

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Comparisons of pharmacokinetic parameters of pantoprazole in domestic animal species, after single dose intravenous administration.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques: