Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(–) electrospray tandem mass spectrometry

Partani, Pankaj; Verma, Saurabh; Gurule, Sanjay; Khuroo, Arshad; Monif, Tausif

doi:10.1016/j.jpha.2013.09.007

Cited by 40 publications

(34 citation statements)

References 29 publications

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“…Quantitative analysis of statins and their metabolites is well documented and several groups have reported the pharmacokinetic profile of orally administered statins in plasma [113–120]. Effective methods employ liquid chromatography-tandem mass spectrometry (LC-MS/MS) for accurate quantification and high sensitivity detection [100–102,113,121].…”

Section: Statin Pharmacological Properties and Drug Metabolism: Ormentioning

confidence: 99%

Innovations in asthma therapy: is there a role for inhaled statins?

Zeki

Elbadawi-Sidhu

2018

Expert Review of Respiratory Medicine

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Introduction Asthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a. statins), suggest a therapeutic role in chronic inflammatory lung diseases. However, despite positive laboratory investigations and promising epidemiological data, clinical trials using statins for the treatment of asthma have yielded conflicting results. Inadequate statin levels in the airway compartment could explain these findings. Areas covered HMGCR is in the mevalonate (MA) pathway and MA signaling is fundamental to lung biology and asthma. This article will discuss clinical trials of oral statins in asthma, review lab investigations relevant to the systemic versus inhaled administration of statins, address the advantages and disadvantages of inhaled statins, and answer the question: is there a role for inhaled statins in the treatment of asthma? Expert commentary If ongoing investigations show that oral administration of statins has no clear clinical benefits, then repurposing statins for delivery via inhalation is a logical next step. Inhalation of statins bypasses first-pass metabolism by the liver, and therefore, allows for delivery of significantly lower doses to the airways at greater potency. Statins could become the next major class of novel inhalers for the treatment of asthma.

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Section: Statin Pharmacological Properties and Drug Metabolism: Ormentioning

confidence: 99%

Innovations in asthma therapy: is there a role for inhaled statins?

Zeki

Elbadawi-Sidhu

2018

Expert Review of Respiratory Medicine

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“…Good chromatographic separation was important since pOH-AT and oOH-AT have the same precursor → ion-product transitions and because of possible acidlactone interconversion. There are some articles describing isocratic separation of some of the investigated compounds, but they do not include investigation of lactone [27], run is 20 min [21], or precipitation of proteins was used instead of SPE [26].…”

Section: Lc-ms/ms Determinationmentioning

confidence: 99%

“…Some of those methods include enzyme inhibition assay [9], radioimmunoassay [10], electrochemical method [11], high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection [12][13][14][15], liquid chromatography-mass spectrometry [16], microbore liquid chromatography/electrospray ionization-tandem mass spectrometry [17], and liquid chromatography-tandem mass spectrometry (LC-MS/MS) [18][19][20][21][22][23][24][25][26][27]. Immunoassay methods lack specificity and, in some cases, are subject to problems with cross-reactive interferences.…”

Section: Introductionmentioning

confidence: 99%

LC—MS/MS method for quantification of atorvastatin, o-hydroxyatorvastatin, p-hydroxyatorvastatin, and atorvastatin lactone in rat plasma

Crevar-Sakač

Vujić

Vujčić

et al. 2016

Acta Chromatographica

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Summary.A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C 18 Analytical, 4.6 × 100 mm (3.5 μm) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 μL min −1 . The column was kept at constant temperature (25 °C), and autosampler tray temperature was set at 4 °C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 → Q3, collision energy) atorvastatin (559.47 → 440.03, 22 eV), atorvastatin lactone (541.36 → 448.02, 19 eV), orthohydroxyatorvastatin (575.20 → 440.18, 20 eV), para-hydroxyatorvastatin (575.54 → 440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL −1 for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL −1 for atorvastatin and atorvastatin lactone with excellent linearity (r 2 ≥ 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL −1 for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL −1 for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.

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“…Most previously reported methods for the simultaneous quantification of AT, o ‐OAT, and p ‐OAT are based on LC–MS/MS due to its greatly improved selectivity and sensitivity compared with LC–UV . The sample preparation techniques most often employed are LLE and SPE because they generate cleaner extracts than protein precipitation (PPT). However, both techniques require complicated extraction steps and are time consuming.…”

Section: Introductionmentioning

confidence: 99%

High‐throughput salting‐out‐assisted liquid–liquid extraction for the simultaneous determination of atorvastatin, ortho‐hydroxyatorvastatin, and para‐hydroxyatorvastatin in human plasma using ultrafast liquid chromatography with tandem mass spectrometry

Yang

Zhou

et al. 2015

J of Separation Science

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A high-throughput, specific, and rapid liquid chromatography with tandem mass spectrometry method was established and validated for the simultaneous determination of atorvastatin and its two major metabolites, ortho-hydroxyatorvastatin and para-hydroxyatorvastatin, in human plasma. A simple salting-out-assisted liquid-liquid extraction using acetonitrile and a mass-spectrometry-friendly salt, ammonium acetate, was employed to extract the analytes from human plasma. A recovery of more than 81% for all analytes was achieved in 1 min extraction time. Chromatographic separation was performed on a Kinetex XB C18 column utilizing a gradient elution starting with a 60% of water solution (1% formic acid), followed by increasing percentages of acetonitrile. Analytes were detected on a tandem mass spectrometer equipped with an electrospray ionization source that was operated in the positive mode, using the transitions of m/z 559.3 → m/z 440.2 for atorvastatin, and m/z 575.3 → m/z 440.2 for both ortho- and para-hydroxyatorvastatin. Deuterium-labeled compounds were used as the internal standards. The method was validated over the concentration ranges of 0.0200-15.0 ng/mL for atorvastatin and ortho-hydroxyatorvastatin, and 0.0100-2.00 ng/mL for para-hydroxyatorvastatin with acceptable accuracy and precision. It was then successfully applied in a bioequivalence study of atorvastatin.

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Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(–) electrospray tandem mass spectrometry

Cited by 40 publications

References 29 publications

Innovations in asthma therapy: is there a role for inhaled statins?

Innovations in asthma therapy: is there a role for inhaled statins?

LC—MS/MS method for quantification of atorvastatin, o-hydroxyatorvastatin, p-hydroxyatorvastatin, and atorvastatin lactone in rat plasma

High‐throughput salting‐out‐assisted liquid–liquid extraction for the simultaneous determination of atorvastatin, ortho‐hydroxyatorvastatin, and para‐hydroxyatorvastatin in human plasma using ultrafast liquid chromatography with tandem mass spectrometry

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