Development and Validation of an LC–MS-MS Method for Determination of Simvastatin and Simvastatin Acid in Human Plasma: Application to a Pharmacokinetic Study

Partani, Pankaj; Verma, Saurabh; Monif, Tausif

doi:10.1093/chromsci/bmw087

Cited by 12 publications

(17 citation statements)

References 25 publications

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“…LC-MS/MS assay methods were reported for the simultaneous analysis of simvastatin and simvastatin acid [11][12][13][14][15][16], but some of these methods had a relatively long run time (10, 8 and 6.4 min [11,13,15]) with larger volume of plasma used (475, 300, 1000, 300 μl [11][12][13]16]), compared to our developed method (5 min run with 200 μl of plasma). Finally, most of these method used solid-phase extraction technique for plasma sample preparation [13][14][15][16], which is labor intensive, more time consuming and costly than the liquid-liquid extraction method we used. Analysis methods for the quantification of ATV and its two active metabolites, 2-OH-ATV and 4-OH-ATV, have been reported [17][18][19][20].…”

Section: Discussionmentioning

confidence: 94%

Simultaneous LC–MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery

El-Zailik

Cheung

Wang

et al. 2019

Journal of Pharmaceutical and Biomedical Analysis

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Statins, HMG-CoA reductase inhibitors, are considered the first line treatment of hyperlipidemia to reduce the risk of atherosclerotic cardiovascular diseases. The prevalence of hyperlipidemia and the risk of atherosclerotic cardiovascular diseases are higher in obese patients. Published methods for the quantification of statins and their active metabolites did not test for matrix effect of or validate the method in hyperlipidemic plasma. A sensitive, specific, accurate, and reliable LC-MS/MS method for the simultaneous quantification of simvastatin (SMV), active metabolite of simvastatin acid (SMV-A), atorvastatin (ATV), active metabolites of 2-hydroxy atorvastatin (2-OH-ATV), 4-hydroxy atorvastatin (4-OH-ATV), and rosuvastatin (RSV) was developed and validated in plasma with low (52-103 mg/dl, < 300 mg/dl) and high (352-403 mg/dl, > 300 mg/dl) levels of triglyceride. The column used in this method was ACQUITY UPLC BEH C18 column (2.1 × 100 mm I.D., 1.7 μm). A gradient elution of mobile phase A (10 mM ammonium formate and 0.04% formic acid in water) and mobile phase B (acetonitrile) was used with a flow rate of 0.4 ml/min and run time of 5 min. The transitions of m/z 436.3 → 285.2 for SMV, m/z 437.2 → 303.2 for SMV-A, m/z 559.2 → 440.3 for ATV, m/z 575.4 → 440.3 for 2-OH-ATV and 4-OH-ATV, m/z 482.3 → 258.1 for RSV, and m/z 412.3 → 224.2 for fluvastatin (internal standard, IS)were determined by Selected Reaction Monitoring (SRM) method to detect transitions ions in the positive ion mode. The assay has a linear range of 0.25 (LLOQ) −100 ng/ml for all six analytes. Accuracy (87-114 %), precision (3-13 %), matrix effect (92-110 %), and extraction recovery (88-100 %) of the assay were within the 15% acceptable limit of FDA Guidelines in variations for plasma with both low and high triglyceride levels. The method was used successfully for the quantification of SMV, ATV, RSV, and their active metabolites in human plasma samples collected *

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Section: Discussionmentioning

confidence: 94%

Simultaneous LC–MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery

El-Zailik

Cheung

Wang

et al. 2019

Journal of Pharmaceutical and Biomedical Analysis

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“…The inter-day precision and accuracy were evaluated by analysing fourteen QC replicates run on four consecutive days. Accuracy is required to be within±15% for QC samples [30]. Recovery was calculated for five spiked POVPC concentrations (0.1, 0.5,1, 2 and 5 ng/ml) within the linear dynamic range, and presented as a percentage of original material.…”

Section: Methodsmentioning

confidence: 99%

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Ademowo

Dias

Milic

et al. 2017

Free Radical Biology and Medicine

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Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay.AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10 mg meso-zeaxanthin, 10 mg lutein, 2 mg zeaxanthin) or placebo (sunflower oil) for six months.The MRM-MS method determined serum POVPC sensitively (from 10 µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=−0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003).In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function.

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“…Recovery was calculated for six replicates of each compound and presented as a percentage of initial material. Precision is required to be within ±15% and accuracy between 85-115% [27] Analysis of POVPC levels…”

Section: Hplc Methods Precision Accuracy and Recoverymentioning

confidence: 99%

“…calibration curves are shown in supplementalTable 1. The accuracy was 90-106% and %CV of 5-7%[27]. The limit of detection (LOD) for lutein, zeaxanthin and the internal standard are 0.1, 0.1 and 0.05µM respectively while the limit of quantification (LOQ) for lutein, zeaxanthin and the internal standard are 0.5, 0.5 and 0.2µM respectively.…”

mentioning

confidence: 92%

Partial Mitigation of Oxidized Phospholipid-Mediated Mitochondrial Dysfunction in Neuronal Cells by Oxocarotenoids

Ademowo

Dias

Diaz-Sanchez

et al. 2020

JAD

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Mitochondria are important (patho)physiological sources of reactive oxygen species (ROS) that mediate mitochondrial dysfunction and phospholipid oxidation; an increase in mitochondrial content of oxidised phospholipid (OxPL) associates with cell death. Previously we showed that the circulating OxPL 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3phosphocholine (POVPC) increases in patients with Alzheimer's disease (AD), and associates with lower plasma antioxidant oxocarotenoids, zeaxanthin and lutein. Since oxocarotenoids are metabolised in mitochondria, we propose that during AD, lower concentrations of mitochondrial zeaxanthin and lutein may result in greater phospholipid oxidation and predispose to neurodegeneration. Here, we have investigated whether non-toxic POVPC concentrations impair mitochondrial metabolism in differentiated (d)SH-SY5Y neuronal cells and whether there is any protective role for oxocarotenoids against mitochondrial dysfunction. After 24 hours, glutathione (GSH) concentration was lower in neuronal cells exposed to POVPC (1-20µM) compared with vehicle control without loss of viability compared to control. However, mitochondrial ROS production (determined by MitoSOX oxidation) was increased by 50% only after 20µM POVPC. Following delivery of lutein (0.1-1µM) and zeaxanthin (0.5-5µM) over 24 hours in vitro, oxocarotenoid recovery from dSH-SY5Y cells was >50%. Coincubation with oxocarotenoids prevented loss of GSH after 1µM but not 20µM POVPC, whereas the increase in ROS production induced by 20µM POVPC was prevented by lutein and zeaxanthin. Mitochondrial uncoupling increases and ATP production is inhibited by 20µM but not 1 µM POVPC; carotenoids protected against uncoupling although did not restore ATP production. In summary, 20µM POVPC induced loss of GSH and a mitochondrial bioenergetic deficit in neuronal cells that was not mitigated by oxocarotenoids.

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Development and Validation of an LC–MS-MS Method for Determination of Simvastatin and Simvastatin Acid in Human Plasma: Application to a Pharmacokinetic Study

Cited by 12 publications

References 25 publications

Simultaneous LC–MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery

Simultaneous LC–MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Partial Mitigation of Oxidized Phospholipid-Mediated Mitochondrial Dysfunction in Neuronal Cells by Oxocarotenoids

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