An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and  Its Metabolites in Plasma

Crevar-Sakač, Milkica; Vujić, Zorica; Brborić, Jasmina; Vesna, Kuntic; Uskoković‐Marković, Snežana

doi:10.3390/molecules18032469

Cited by 8 publications

(7 citation statements)

References 23 publications

(24 reference statements)

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“…Atorvastatin (ATR) inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme found in liver tissue that plays a key role in cholesterol production [22]. ATR is commonly used in hyperlipidemia and cardiovascular events.…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin

et al. 2015

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Abstract:The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process), attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution-a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin.

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Section: Introductionmentioning

confidence: 99%

Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin

et al. 2015

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“…), being o‐ATV levels in plasma similar to those of ATV (Crevar‐Sakač et al . ). Thus, since lipophilic statins such ATV are known to easily cross the blood‐brain barrier, we also tested 600 nM ATV and o‐ATV in our neuronal cultures in vitro .…”

Section: Methodsmentioning

confidence: 97%

Specific rescue by ortho‐hydroxy atorvastatin of cortical GABAergic neurons from previous oxygen/glucose deprivation: role of pCREB

Guirao

Martí-Sistac

DeGregorio-Rocasolano

et al. 2017

Journal of Neurochemistry

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The statin atorvastatin (ATV) given as a post-treatment has been reported beneficial in stroke, although the mechanisms involved are not well understood so far. Here, we investigated in vitro the effect of post-treatment with ATV and its main bioactive metabolite ortho-hydroxy ATV (o-ATV) on neuroprotection after oxygen and glucose deprivation (OGD), and the role of the pro-survival cAMP response element-binding protein (CREB). Post-OGD treatment of primary cultures of rat cortical neurons with o-ATV, but not ATV, provided neuroprotection to a specific subset of cortical neurons that were large and positive for glutamic acid decarboxylase (large-GAD neurons, GABAergic). Significantly, only these GABAergic neurons showed an increase in phosphorylated CREB (pCREB) early after neuronal cultures were treated post-OGD with o-ATV. We found that o-ATV, but not ATV, increased the neuronal uptake of glutamate from the medium; this provides a rationale for the specific effect of o-ATV on pCREB in large-GABAergic neurons, which have a higher ratio of synaptic (pCREB-promoting) vs extrasynaptic (pCREB-reducing) N-methyl-D-aspartate (NMDA) receptors (NMDAR) than that of small-non-GABAergic neurons. When we pharmacologically increased pCREB levels post-OGD in non-GABAergic neurons, through the selective activation of synaptic NMDAR, we observed as well long-lasting neuronal survival. We propose that the statin metabolite o-ATV given post-OGD boosts the intrinsic pro-survival factor pCREB in large-GABAergic cortical neurons in vitro, this contributing to protect them from OGD.

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“…Table 1 enlist the various HPLC methods coupled with UV, DAD, and PDA detectors used to detect AT and co-administered drugs in biological fluids. Usually, the reverse phase HPLC method has been used to quantify AT using C18 analytical columns because of the presence of pyrrole and phenyl as aromatic functional groups that make analysis suitable by the reverse phase method [52]. However, some published work has used the C8 column as the stationary phase.…”

Section: Analysis Using Hplcmentioning

confidence: 99%

“…The mobile phase that has been used in the quantification of AT in biological matrices, primarily comprised of acetonitrile (ACN), methanol (MeOH), water, and different buffer solutions that have either isocratic or gradient elution with a flow rate of 1 mL min −1 . Retention of analyte in the analytical column hinge upon the pH of elution, so in reported bioanalytical assays, pH of the mobile phase has been maintained between 2 and 4 to make better retention of analyte in the analytical column and enhanced the resolution of the peak because these pH values are lesser than pKa value of AT and AT remain in unionized form for a longer time and interact more with the stationary phase [52]. The retention time (R t ) of AT reported in Table 1 variegates from 1.7 to 19.8 min, but in most of the developed HPLC methods, R t has ranged 2 to 5 min.…”

Section: Analysis Using Hplcmentioning

confidence: 99%

“…Interestingly, a study by Partani et al concluded that analysis in ESI − mode gives quite low LOQ value because the negative ions enhance the selective detection and also improve the sensitivity of the method [67]. Principally, quantification of AT has been carried out using multiple reaction monitoring (MRM) transition with the precursor ion M+H + at m/z 559 Da and product ion at m/z 440 Da, while SRM transition has also been employed in numerous ESI + methods with transitions at m/z 559 → 440 [52,65,70,81,88,89]. Importantly, Jang et al utilized the MRM transition of m/z 559.3 → 250.2 for the detection of AT in the human urine samples [92].…”

Section: Analysis Using Lc-ms/ms and Uplc-ms/msmentioning

confidence: 99%

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A review on liquid chromatographic methods for the bioanalysis of atorvastatin

Wadhwa

Rana

2021

Futur J Pharm Sci

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Background The unsatisfied clinical need has encouraged the development and validation of bioanalytical procedures for the quantification of drugs in biological samples because the monitoring of drug concentrations helps in personalizing the patient’s pharmacotherapy, assessing the adherence to therapy, and is also extensively useful for pharmacokinetics and drug-drug interactions studies. Main Body The present review aimed to provide insightful information about the various liquid chromatographic methods developed till 2019 for the analysis and quantification of atorvastatin, its metabolites, and co-administered drugs in the various biological matrices like the serum, plasma, and urine with special emphasis on sample preparation techniques applied before chromatographic analysis along with different chromatographic conditions and their validation data. A total of 88 published papers that have used liquid chromatography techniques to quantify atorvastatin in biological fluids are included in the study. Out of the total reported liquid chromatographic methods, 34% used UV spectrophotometer as a detector, and 55% used MS/MS as a detector. Whereas 38% of them used protein precipitation procedure, 33% applied liquid-liquid extraction approach, and 12% employed solid-phase extraction technique for sample preparation. Conclusion In the last decade, numerous bioanalytical procedures have been developed for the quantification of atorvastatin in different biological samples using liquid chromatographic techniques. Moreover, advancement in technology developed several new and advanced sample preparation approaches like dispersive liquid-liquid extraction, microextraction by packed sorbent, which have high recovery rates than conventional procedures. Thus, the summarized review may be consulted as an informative tool to support the optimization of new bioanalytical methods for the quantification of atorvastatin.

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An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma

Cited by 8 publications

References 23 publications

Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin

Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin

Specific rescue by ortho‐hydroxy atorvastatin of cortical GABAergic neurons from previous oxygen/glucose deprivation: role of pCREB

A review on liquid chromatographic methods for the bioanalysis of atorvastatin

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