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simvastatin hydroxy acid d6 ammonium salt sva d6  (Toronto Research Chemicals)


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    Toronto Research Chemicals simvastatin hydroxy acid d6 ammonium salt sva d6
    Simvastatin Hydroxy Acid D6 Ammonium Salt Sva D6, supplied by Toronto Research Chemicals, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/simvastatin+acid+sva/Acid+Blue+9/pm34942336-91-9-29
    Average 90 stars, based on 1 article reviews
    simvastatin hydroxy acid d6 ammonium salt sva d6 - by Bioz Stars, 2026-10
    90/100 stars

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    Article Title: A Simple Protein Precipitation-based Simultaneous Quantification of Lovastatin and Its Active Metabolite Lovastatin Acid in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry using Polarity Switching
    Article Snippet: LVA, simvastatin (SV) and simvastatin acid (SVA) were obtained from Toronto Research Chemicals Inc. (North York, ON, Canada).



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    Toronto Research Chemicals simvastatin hydroxy acid ammonium salt sva
    Interconversion of <t>simvastatin</t> and pravastatin between lactone and hydroxy acid forms in human plasma of different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test (*** P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.
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    Toronto Research Chemicals simvastatin acid sva
    Interconversion of <t>simvastatin</t> and pravastatin between lactone and hydroxy acid forms in human plasma of different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test (*** P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.
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    Interconversion of simvastatin and pravastatin between lactone and hydroxy acid forms in human plasma of different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test (*** P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Interconversion of simvastatin and pravastatin between lactone and hydroxy acid forms in human plasma of different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test (*** P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Clinical Proteomics, Incubation, Modification, Concentration Assay, Standard Deviation

    Interconversion of statins between lactone and hydroxy acid forms in phosphate buffer saline at different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with PBS of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of the lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test ( ∗∗∗ P < 0.001; ** P < 0.01). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Interconversion of statins between lactone and hydroxy acid forms in phosphate buffer saline at different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with PBS of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of the lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test ( ∗∗∗ P < 0.001; ** P < 0.01). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Saline, Incubation, Modification, Concentration Assay, Standard Deviation

    Interconversion of statins between lactone and hydroxy acid forms in Dulbecco's modified eagle medium culture medium at different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with Dulbecco's modified eagle medium culture medium of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of the lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test ( ∗∗∗ P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Interconversion of statins between lactone and hydroxy acid forms in Dulbecco's modified eagle medium culture medium at different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with Dulbecco's modified eagle medium culture medium of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of the lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test ( ∗∗∗ P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Modification, Incubation, Concentration Assay, Standard Deviation

    Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in human plasma at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL ( A ) and formation of simvastatin hydroxy acid form ( B ). a = pH 7.0 vs pH 7.6 ( P < 0.05); pH 7.4 vs pH 6.8, 7.8 ( P < 0.01); pH 6.8 vs pH 7.6, 7.8; pH 7.8 vs pH 7.0, 7.2 ( P < 0.001). b = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 ( P < 0.001); pH 7.6 vs pH 7.8 ( P < 0.05). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.6 ( P < 0.05). e = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.2, 7.8 ( P < 0.05). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 7.6 vs pH 6.8, 7.4 ( P < 0.01); pH 7.8 vs pH 6.8, 7.0, 7.2, 7.4; pH 7.2 vs pH 7.6 ( P < 0.001). b = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.0 vs pH 7.2 ( P < 0.01).

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in human plasma at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL ( A ) and formation of simvastatin hydroxy acid form ( B ). a = pH 7.0 vs pH 7.6 ( P < 0.05); pH 7.4 vs pH 6.8, 7.8 ( P < 0.01); pH 6.8 vs pH 7.6, 7.8; pH 7.8 vs pH 7.0, 7.2 ( P < 0.001). b = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 ( P < 0.001); pH 7.6 vs pH 7.8 ( P < 0.05). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.6 ( P < 0.05). e = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.2, 7.8 ( P < 0.05). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 7.6 vs pH 6.8, 7.4 ( P < 0.01); pH 7.8 vs pH 6.8, 7.0, 7.2, 7.4; pH 7.2 vs pH 7.6 ( P < 0.001). b = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.0 vs pH 7.2 ( P < 0.01).

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Clinical Proteomics, Incubation, Modification, Concentration Assay, Standard Deviation

    Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in phosphate buffer saline at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with phosphate buffer saline of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL ( A ) and formation of simvastatin hydroxy acid form ( B ). a = pH 7.8 vs pH 6.8, 7.0 ( P < 0.001); pH 7.8 vs pH 7.2 ( P < 0.05). b = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001); pH 7.2 vs pH 7.4 ( P < 0.05). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001); pH 7.4 vs pH 7.6 ( P < 0.01); pH 7.6 vs pH 7.8 ( P < 0.05). e = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05). f = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001). g = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8 ( P < 0.001). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 6.8 vs pH 7.6, 7.8; pH 7.0 vs pH 7.6, 7.8; pH 7.2 vs pH 7.8 ( P < 0.001); pH 7.4 vs pH 6.8, 7.8; pH 7.2 vs pH 7.6 ( P < 0.01); pH 7.0 vs pH 7.4 ( P < 0.05). b = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 ( P < 0.001); pH 7.0 vs pH 7.2 ( P < 0.01). c = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 6.8 vs pH 7.0 ( P < 0.01); pH 7.4 vs pH 7.6 ( P < 0.05). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001). e = 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8, ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); pH 7.2 vs pH 7.4 ( P < 0.05). f = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8 ( P < 0.001). g = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8 ( P < 0.001).

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in phosphate buffer saline at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with phosphate buffer saline of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL ( A ) and formation of simvastatin hydroxy acid form ( B ). a = pH 7.8 vs pH 6.8, 7.0 ( P < 0.001); pH 7.8 vs pH 7.2 ( P < 0.05). b = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001); pH 7.2 vs pH 7.4 ( P < 0.05). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001); pH 7.4 vs pH 7.6 ( P < 0.01); pH 7.6 vs pH 7.8 ( P < 0.05). e = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05). f = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001). g = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8 ( P < 0.001). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 6.8 vs pH 7.6, 7.8; pH 7.0 vs pH 7.6, 7.8; pH 7.2 vs pH 7.8 ( P < 0.001); pH 7.4 vs pH 6.8, 7.8; pH 7.2 vs pH 7.6 ( P < 0.01); pH 7.0 vs pH 7.4 ( P < 0.05). b = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 ( P < 0.001); pH 7.0 vs pH 7.2 ( P < 0.01). c = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 6.8 vs pH 7.0 ( P < 0.01); pH 7.4 vs pH 7.6 ( P < 0.05). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001). e = 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8, ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); pH 7.2 vs pH 7.4 ( P < 0.05). f = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8 ( P < 0.001). g = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8 ( P < 0.001).

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Saline, Incubation, Modification, Concentration Assay, Standard Deviation

    Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in Dulbecco's modified eagle medium culture medium at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with Dulbecco's modified eagle mediumculture medium of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL ( A ) and formation of simvastatin hydroxy acid form ( B ). a = pH 7.8 vs pH 6.8, 7.2 ( P < 0.01). b = pH 6.8 vs pH 7.2 ( P < 0.05); pH 6.8 vs pH 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). c = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8; pH 7.4 vs 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs 7.8 ( P < 0.01). e = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8 ( P < 0.001). f = pH 6.8 vs pH 7.2, 7.4, 7.8 ( P < 0.001). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 6.8 vs pH 7.8 ( P < 0.01); pH 7.2 vs pH 7.8 ( P < 0.05). b = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.8 vs pH 7.2, 7.4 ( P < 0.001). c = 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs 7.8 ( P < 0.001); pH 7.2 vs pH 7.4 ( P < 0.05). d = pH 6.8 vs pH 7.2, 7.4, 7.8 ( P < 0.001). e = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 6.8 vs pH 7.2 ( P < 0.05).

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in Dulbecco's modified eagle medium culture medium at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with Dulbecco's modified eagle mediumculture medium of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL ( A ) and formation of simvastatin hydroxy acid form ( B ). a = pH 7.8 vs pH 6.8, 7.2 ( P < 0.01). b = pH 6.8 vs pH 7.2 ( P < 0.05); pH 6.8 vs pH 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). c = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8; pH 7.4 vs 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs 7.8 ( P < 0.01). e = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8 ( P < 0.001). f = pH 6.8 vs pH 7.2, 7.4, 7.8 ( P < 0.001). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 6.8 vs pH 7.8 ( P < 0.01); pH 7.2 vs pH 7.8 ( P < 0.05). b = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.8 vs pH 7.2, 7.4 ( P < 0.001). c = 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs 7.8 ( P < 0.001); pH 7.2 vs pH 7.4 ( P < 0.05). d = pH 6.8 vs pH 7.2, 7.4, 7.8 ( P < 0.001). e = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 6.8 vs pH 7.2 ( P < 0.05).

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Modification, Incubation, Concentration Assay, Standard Deviation

    The pH dependence of the hydrolysis of the lactone form of statins

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: The pH dependence of the hydrolysis of the lactone form of statins

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Clinical Proteomics

    Liver microsomal stability of simvastatin lactone at 3 different pH levels. ( A ) Microsomal stability of simvastatin lactone as a function of time at different pH levels; ( B ) concentration-time profiles of simvastatin hydroxy acid form detected in liver microsomal stability reaction mixtures at 3 different pH levels. Results are expressed as mean ± standard deviation, (n = 3). Solid line denotes exponential regression of samples at pH 6.8; dashed line denotes exponential regression of samples at pH 7.4; whereas dotted line denotes exponential regression samples at pH 7.8.

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Liver microsomal stability of simvastatin lactone at 3 different pH levels. ( A ) Microsomal stability of simvastatin lactone as a function of time at different pH levels; ( B ) concentration-time profiles of simvastatin hydroxy acid form detected in liver microsomal stability reaction mixtures at 3 different pH levels. Results are expressed as mean ± standard deviation, (n = 3). Solid line denotes exponential regression of samples at pH 6.8; dashed line denotes exponential regression of samples at pH 7.4; whereas dotted line denotes exponential regression samples at pH 7.8.

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Concentration Assay, Standard Deviation

    Uptake of simvastatin lactone (SVL) and simvastatin hydroxy acid (SVA) by undifferentiated and differentiated C2C12 cells. The uptake was determined after incubation of the cells with 1 μmol/L of SVL or SVA in Dulbecco's modified eagle medium culture medium of different pH levels (6.8–7.8) at 37°C for 6 hours. Results are expressed as nanomoles per milligram of protein ±standard deviation, (n = 5). Data were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) Total simvastatin (lactone + hydroxy acid) recovered by undifferentiated C2C12 cells after treatment with 1 μmol/L SVL. a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.8 ( P < 0.05). ( B ) Total simvastatin recovered by differentiated C2C12 cells after treatment with 1 μmol/L SVL. a = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); b = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.01). ( C ) SVA recovered by undifferentiated C2C12 cells after treatment with 1 μmol/L SVA (no SVL was recovered in this experiment). a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001). ( D ) Total simvastatin recovered by differentiated C2C12 cells after treatment with 1 μmol/L SVA. a = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); d = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001).

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Uptake of simvastatin lactone (SVL) and simvastatin hydroxy acid (SVA) by undifferentiated and differentiated C2C12 cells. The uptake was determined after incubation of the cells with 1 μmol/L of SVL or SVA in Dulbecco's modified eagle medium culture medium of different pH levels (6.8–7.8) at 37°C for 6 hours. Results are expressed as nanomoles per milligram of protein ±standard deviation, (n = 5). Data were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) Total simvastatin (lactone + hydroxy acid) recovered by undifferentiated C2C12 cells after treatment with 1 μmol/L SVL. a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.8 ( P < 0.05). ( B ) Total simvastatin recovered by differentiated C2C12 cells after treatment with 1 μmol/L SVL. a = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); b = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.01). ( C ) SVA recovered by undifferentiated C2C12 cells after treatment with 1 μmol/L SVA (no SVL was recovered in this experiment). a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001). ( D ) Total simvastatin recovered by differentiated C2C12 cells after treatment with 1 μmol/L SVA. a = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); d = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001).

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Incubation, Modification, Standard Deviation

    Uptake of simvastatin by undifferentiated and differentiated C2C12 cells. The uptake was determined after incubation of the cells with 1 μmol/L of simvastatin lactone (SVL) or simvastatin hydroxy acid (SVA) in Dulbecco's modified eagle medium of different pH levels (6.8–7.8) at 37°C for 6 hours. Results are expressed as nanomoles per milligram of protein ± standard deviation, (n = 5). Data were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) Intracellular concentration of simvastatin acid and lactone recovered from undifferentiated cells after treatment with 1 μmol/L SVL. a = SVL, pH 6.8 vs SVA, pH 6.8; SVL, pH 7.4 vs SVA, pH 7.4 ( P < 0.001); b = SVL, pH 6.8 vs SVA, pH 6.8; SVL, pH 7.4 vs SVA, pH 7.4; SVL, pH 7.8 vs SVA, pH 7.8 ( P < 0.001); c = SVL, pH 6.8 vs SVA, pH 6.8; SVL, pH 7.4 vs SVA, pH 7.4 ( P < 0.001); SVL, pH 7.8 vs SVA, pH 7.8 ( P < 0.01). ( B ) Intracellular concentration of simvastatin acid and lactone recovered from differentiated cells after treatment with 1 μmol/L SVL. a = SVL, pH 6.8 vs SVA, pH 6.8 ( P < 0.001). ( C ) Intracellular concentration of simvastatin acid and lactone recovered from differentiated cells after treatment with 1 μmol/L SVA. a = SVA, pH 6.8 vs SVL, pH 6.8; SVA, pH 7.4 vs SVL, pH 7.4 ( P < 0.001); b = SVA, pH 6.8 vs SVL, pH 6.8; SVA, pH 7.4 vs SVL, pH 7.4; SVA, pH 7.8 vs SVL, pH 7.8 ( P < 0.001); c = SVA, pH 6.8 vs SVL, pH 6.8; SVA, pH 7.4 vs SVL, pH 7.4 ( P < 0.001); SVA, pH 7.8 vs SVL, pH 7.8 ( P < 0.01).

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Uptake of simvastatin by undifferentiated and differentiated C2C12 cells. The uptake was determined after incubation of the cells with 1 μmol/L of simvastatin lactone (SVL) or simvastatin hydroxy acid (SVA) in Dulbecco's modified eagle medium of different pH levels (6.8–7.8) at 37°C for 6 hours. Results are expressed as nanomoles per milligram of protein ± standard deviation, (n = 5). Data were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) Intracellular concentration of simvastatin acid and lactone recovered from undifferentiated cells after treatment with 1 μmol/L SVL. a = SVL, pH 6.8 vs SVA, pH 6.8; SVL, pH 7.4 vs SVA, pH 7.4 ( P < 0.001); b = SVL, pH 6.8 vs SVA, pH 6.8; SVL, pH 7.4 vs SVA, pH 7.4; SVL, pH 7.8 vs SVA, pH 7.8 ( P < 0.001); c = SVL, pH 6.8 vs SVA, pH 6.8; SVL, pH 7.4 vs SVA, pH 7.4 ( P < 0.001); SVL, pH 7.8 vs SVA, pH 7.8 ( P < 0.01). ( B ) Intracellular concentration of simvastatin acid and lactone recovered from differentiated cells after treatment with 1 μmol/L SVL. a = SVL, pH 6.8 vs SVA, pH 6.8 ( P < 0.001). ( C ) Intracellular concentration of simvastatin acid and lactone recovered from differentiated cells after treatment with 1 μmol/L SVA. a = SVA, pH 6.8 vs SVL, pH 6.8; SVA, pH 7.4 vs SVL, pH 7.4 ( P < 0.001); b = SVA, pH 6.8 vs SVL, pH 6.8; SVA, pH 7.4 vs SVL, pH 7.4; SVA, pH 7.8 vs SVL, pH 7.8 ( P < 0.001); c = SVA, pH 6.8 vs SVL, pH 6.8; SVA, pH 7.4 vs SVL, pH 7.4 ( P < 0.001); SVA, pH 7.8 vs SVL, pH 7.8 ( P < 0.01).

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Incubation, Modification, Standard Deviation, Concentration Assay

    Effect of simvastatin lactone (SVL) and simvastatin hydroxy acid (SVA) on the viability of undifferentiated and differentiated C2C12. Cells were cultured at a density of 4,000 cells/well and allowed to attach for 24 hours or to differentiate for 4 days, then exposed to increasing concentrations of SVL or SVA under acidic, neutral, and alkaline medium pH for 72 hours. Results are presented as mean ± standard deviation of 3 experiments, 8 replicates per experiment. Data were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) Effects of SVL on cell viability of undifferentiated C2C12 myoblasts. a = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001); b = pH 7.8 vs pH 6.8, 7.4; pH 6.8 vs pH 7.4 ( P < 0.001). ( B ) Effects of SVL on cell viability of differentiated C2C12 myocytes. a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); d = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); e = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001). ( C ) Effects of SVA on cell viability of undifferentiated C2C12 myoblasts. a = pH 6.8 vs pH 7.4 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); b = pH 7.8 vs pH 6.8, 7.4 ( P < 0.05); c = pH 7.4 vs pH 7.8 ( P < 0.01); d = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001); e = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( D ) Effects of SVA on cell viability of differentiated C2C12 myocytes. a = pH 6.8 vs pH 7.8 ( P < 0.001); b = pH 7.4 vs pH 6.8, 7.8 ( P < 0.05); pH 6.8 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); d = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); e = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001).

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Effect of simvastatin lactone (SVL) and simvastatin hydroxy acid (SVA) on the viability of undifferentiated and differentiated C2C12. Cells were cultured at a density of 4,000 cells/well and allowed to attach for 24 hours or to differentiate for 4 days, then exposed to increasing concentrations of SVL or SVA under acidic, neutral, and alkaline medium pH for 72 hours. Results are presented as mean ± standard deviation of 3 experiments, 8 replicates per experiment. Data were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) Effects of SVL on cell viability of undifferentiated C2C12 myoblasts. a = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001); b = pH 7.8 vs pH 6.8, 7.4; pH 6.8 vs pH 7.4 ( P < 0.001). ( B ) Effects of SVL on cell viability of differentiated C2C12 myocytes. a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); d = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); e = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001). ( C ) Effects of SVA on cell viability of undifferentiated C2C12 myoblasts. a = pH 6.8 vs pH 7.4 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); b = pH 7.8 vs pH 6.8, 7.4 ( P < 0.05); c = pH 7.4 vs pH 7.8 ( P < 0.01); d = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001); e = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( D ) Effects of SVA on cell viability of differentiated C2C12 myocytes. a = pH 6.8 vs pH 7.8 ( P < 0.001); b = pH 7.4 vs pH 6.8, 7.8 ( P < 0.05); pH 6.8 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); d = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); e = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001).

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Cell Culture, Standard Deviation

    Cytotoxicity of statins to C2C12 cells after 72 hours of treatment in medium of different pH. Data are presented as mean ± SD of 3 experiments, 8 replicates per experiment

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Cytotoxicity of statins to C2C12 cells after 72 hours of treatment in medium of different pH. Data are presented as mean ± SD of 3 experiments, 8 replicates per experiment

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques:

    Effect of simvastatin lactone (SVL) and simvastatin hydroxy acid (SVA) on lactate dehydrogenase (LDH) release from undifferentiated and differentiated C2C12 cells maintained under different pH levels. C2C12 cells were cultured at a density of 4,000 cells/well and allowed to attach for 24 hours or to differentiate for 4 days, then exposed to increasing concentrations of SVL or SVA under acidic, neutral, and alkaline medium pH. Undifferentiated cells were treated for 72 hours, whereas differentiated cells were maintained for 24 hours. Data are presented as mean ± standard deviation, (n = 3) and analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) LDH release from undifferentiated C2C12 cells treated with SVL. a = pH 6.8 vs pH 7.4 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( B ) LDH release from differentiated C2C12 cells treated with SVL. a = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( C ) LDH release from undifferentiated C2C12 cells treated with SVA. a = pH 6.8 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4 ( P < 0.01); pH 7.8 vs pH 6.8, 7.4 ( P < 0.001). ( D ) LDH release from differentiated C2C12 cells treated with SVA. a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.0001).

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Effect of simvastatin lactone (SVL) and simvastatin hydroxy acid (SVA) on lactate dehydrogenase (LDH) release from undifferentiated and differentiated C2C12 cells maintained under different pH levels. C2C12 cells were cultured at a density of 4,000 cells/well and allowed to attach for 24 hours or to differentiate for 4 days, then exposed to increasing concentrations of SVL or SVA under acidic, neutral, and alkaline medium pH. Undifferentiated cells were treated for 72 hours, whereas differentiated cells were maintained for 24 hours. Data are presented as mean ± standard deviation, (n = 3) and analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) LDH release from undifferentiated C2C12 cells treated with SVL. a = pH 6.8 vs pH 7.4 ( P < 0.001); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( B ) LDH release from differentiated C2C12 cells treated with SVL. a = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( C ) LDH release from undifferentiated C2C12 cells treated with SVA. a = pH 6.8 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4 ( P < 0.01); pH 7.8 vs pH 6.8, 7.4 ( P < 0.001). ( D ) LDH release from differentiated C2C12 cells treated with SVA. a = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.0001).

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Cell Culture, Standard Deviation

    Intraday and interday precision and accuracy of HPLC methods used for determination of statins in human plasma samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Intraday and interday precision and accuracy of HPLC methods used for determination of statins in human plasma samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Clinical Proteomics, Concentration Assay, Control

    Intraday and interday precision and accuracy of HPLC methods used for determination statins in PBS samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Intraday and interday precision and accuracy of HPLC methods used for determination statins in PBS samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Concentration Assay, Control

    Intraday and interday precision and accuracy of HPLC methods used for determination of statins in DMEM culture medium samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Intraday and interday precision and accuracy of HPLC methods used for determination of statins in DMEM culture medium samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Concentration Assay, Control

    Intraday and interday precision and accuracy of LC MS/MS methods used for determination of statins in cell lysate samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Intraday and interday precision and accuracy of LC MS/MS methods used for determination of statins in cell lysate samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Concentration Assay, Control

    Extraction recovery (%) of statins from human plasma, PBS, and DMEM samples

    Journal: Translational Research

    Article Title: The role of acid-base imbalance in statin-induced myotoxicity

    doi: 10.1016/j.trsl.2016.03.015

    Figure Lengend Snippet: Extraction recovery (%) of statins from human plasma, PBS, and DMEM samples

    Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).

    Techniques: Extraction, Clinical Proteomics, Control