Methanolic extract of S. securidaca flowers, leaves, and seeds' antihyperlipidemic effects on high fat diet-induced hyperlipidemia in Wistar rats.

Significant risk factors for atherosclerosis include hyperlipidemia and oxidative stress, which together rank as three of the most significant risk factors for cardiovascular diseases. Securigera securidaca lowers cholesterol levels in diabetic rats' blood. This investigation's objective was to determine how methanolic extracts affected the flowers, leaves, and seeds of plants in rats that were fed a high-fat diet (HFD). Five groups of animals were created (n = 5). A total of 35 days, divided into two intervals, were used for the study. Rats received HFD during the first 15-day interval, while during the second 20-day interval, they also received extracts or the Atorvastatin reference drug. The extract of seeds has a high phenol content as well as DPPH radical antioxidant activity. Extracts were given at a dose of 200 mg/kg; p.o. Methanolic treatment of S. securidaca flowers, leaves, and seeds in HFD-induced hyperlipidemic rats resulted in significant reductions in total cholesterol, triglycerides, LDLC, and VLDL-C levels. HDL-C levels increased significantly because of the leaves. While in hyperlipidemic rats, seeds significantly reduced the activities of the enzymes ALT and ALP. The findings showed that, to a certain extent, seeds, flowers, and leaves may have benefits in reducing hyperlipidemia brought on by HFD in terms of lipid profiles and liver function enzymes. The findings of this study indicate a promising application prospect, but more research is needed to determine the exact mechanism of these novel compounds as antihyperlipidemic agents and to clarify their potential combination effect with synthetic drugs such as Atorvastatin. Combinations can reduce the dose of chemical medications required, which lowers the risk of side effects.

[18F]Atorvastatin Pharmacokinetics and Biodistribution in Healthy Female and Male Rats.

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that are widely used to prevent cardiovascular diseases. However, a series of pleiotropic mechanisms have been associated with statins, particularly with atorvastatin. Therefore, the assessment of [18F]atorvastatin kinetics with positron emission tomography (PET) may elucidate the mechanism of action of statins and the impact of sexual dimorphism, which is one of the most debated interindividual variations influencing the therapeutic efficacy. [18F]Atorvastatin was synthesized via a previously optimized 18F-deoxyfluorination strategy, used for preclinical PET studies in female and male Wistar rats (n = 7 for both groups), and for subsequent ex vivo biodistribution assessment. PET data were fitted to several pharmacokinetic models, which allowed for estimating relevant kinetic parameters. Both PET imaging and biodistribution studies showed negligible uptake of [18F]atorvastatin in all tissues compared with the primary target organ (liver), excretory pathways (kidneys and small intestine), and stomach. Uptake of [18F]atorvastatin was 38 ± 3% higher in the female liver than in the male liver. The irreversible 2-tissue compartment model showed the best fit to describe [18F]atorvastatin kinetics in the liver. A strong correlation (R2 > 0.93) between quantitative Ki (the radiotracer's unidirectional net rate of influx between compartments) and semi-quantitative liver's SUV (standard uptake value), measured between 40 to 90 min, showed potential to use the latter parameter, which circumvents the need for blood sampling as a surrogate of Ki for monitoring [18F]atorvastatin uptake. Preclinical assays showed faster uptake and clearance for female rats compared to males, seemingly related to a higher efficiency for exchanges between the arterial input and the hepatic tissue. Due to the slow [18F]atorvastatin kinetics, equilibrium between the liver and plasma concentration was not reached during the time frame studied, making it difficult to obtain sufficient and accurate kinetic information to quantitatively characterize the radiotracer pharmacokinetics over time. Nevertheless, the reported results suggest that the SUV can potentially be used as a simplified measure, provided all scans are performed at the same time point. Preclinical PET-studies with [18F]atorvastatin showed faster uptake and clearance in female compared to male rats, apparently related to higher efficiency for exchange between arterial blood and hepatic tissue.

Sustainable environment-friendly quantitative determination of three anti-hyperlipidemic statin drugs and ezetimibe in binary mixtures by first derivative Fourier transform infrared (FTIR) spectroscopy.

FTIR spectrometry is considered a sustainable green analytical chemistry procedure. Its use in quantitative analysis of pharmaceutical compounds in their raw resources and in their dosage forms is growing currently. The current research offers an environment-friendly, speedy, cost-effective, reliable and easy method for the simultaneous estimation of anti-hyperlipidemic drugs. No sample preparation was required except for grinding and mixing with KBr for making pellets used for acquisition of the FT-IR spectra. First-derivative FTIR spectroscopy is used to assess quantitatively atorvastatin (ATR), rosuvastatin (RSV) and simvastatin (SMV) in their binary mixtures with ezetimibe (EZT). For the first mixture, EZT and ATR were determined at 1733.18 cm-1 and 1647.74 cm-1, respectively. In the second mixture, the zero-crossing wave numbers selected for the determination of EZT and RSV were 1733.18 cm-1 and 955.69 cm-1, correspondingly. Whereas, the third mixture was quantified at the wavenumbers of 1520.93 and 3569.68 cm-1 for EZT and SMV, respectively. Validation of the procedure has been performed complying with recommendations of the International Conference of Harmonization (ICH) presenting linearity, accuracy, precision, robustness and selectivity. The linear range for all drugs was 2-30 mg/g. It was found that the LOD was 0.607, 0.311, 0.491 and 0.395 mg/g and the LOQ was found to be 1.839, 0.942, 1.490 and 1.190 mg/g for EZT, ATR, RSV, and SMV, correspondingly. The proposed technique was found to be accurate and precise in terms of percentage error and percentage relative standard deviation among intraday and interday measurements. It was also found selective through comparison of the results of standard drugs with results of binary mixtures and of pharmaceutical tablets. It was found robust through making slight variations in the working conditions and the results obtained remained statistically equivalent. The technique was applied effectively for the estimation of the binary mixtures under study in their tablets. Comparing the found outcomes to those of reference derivative UV spectrophotometric methods gave no significant difference between them. Analytical eco-scale and the scale of Green Analytical Procedure Index (GAPI) are the two scales utilized for evaluation of the greenness of the technique and it was found to be excellent green.

A novel HPLC method developed and validated for the detection and quantification of atorvastatin, fluvastatin, pitavastatin and pravastatin during transdermal delivery studies.

An HPLC method was developed and validated to quantify and identify several statins (atorvastatin, fluvastatin, pitavastatin and pravastatin) that were used during transdermal drug delivery. The method proved to be most effective with a Restek Ultra C18, 250 x 4.6 mm, 5 µm column, a flow rate of 1.0 ml/min, UV detection at 240 nm and injection volume of 10 µl. The mobile phase used was acetonitrile/Milli-Q® water with 0.1% orthophosphoric acid starting with 30% acetonitrile, which increased linearly to 70% (after 4 min) for up to 10 min and then re-equilibrated to start conditions. This HPLC method indicated linearity (correlation coefficient (R²) of 1) within the concentration range of 0.05-200.00 µg/ml and had an average recovery of 98-103%. Limit of detection (LOD) and limit of quantification (LOQ) showed that statins could still be identified at concentrations of 0.004-0.006 µg/ml with the exception of atorvastatin (quantifiable at 0.013-0.035 µg/ml). Specificity performed during method validation, confirmed that the method was suitable for accurate detection and quantification of the statins when included in the transdermal formulations with other excipients.

Sensitive fluorescence detection of atorvastatin by doped carbon dots synthesized in deep eutectic media.

Fluorescence properties of nanoparticles can be influenced by solvent. In this work, carbon dots (CDs) were synthesized in deep eutectic solvent by microwave assisted method. Quantum yield (QY) and size of the synthesized CDs were 41.3% and 2 nm, respectively. N/Cl -doped CDs had excellent sensitivity and selectivity for atorvastatin and detection limit was 0.8 nM. Simple and low-cost synthesis method and excellent sensitivity are advantages of this detection method for atorvastatin. The as-synthesized N/Cl-doped CDs were successfully used to determine atorvastatin in blood serum.

First-derivative synchronous spectrofluorimetric method for estimation of losartan potassium and atorvastatin in their pure forms and in tablets.

Losartan potassium (LOS) and atorvastatin (ATR) are used in combination for long-term treatment of stroke and for treatment of hypertension with high-level cholesterol. Both drugs were simultaneously determined and validated using a novel, easy, fast, and economical first-derivative synchronous fluorescence spectroscopic method. Methanol was used as the solvent for both drugs at a Δλ 80 nm and with a scanning rate of 600 nm/min. Peaks were determined as at 288.1 nm and 263.6 nm for LOS and ATR, respectively. The proposed method was validated according to International Conference on Harmonization guidelines and, subsequently, the developed method was applicable to the analysis of the two compounds in their different formulations without interference from each other. Amplitude-concentration plots were rectilinear over the concentration ranges 1.0-10.0 µg/ml and 0.5-5.0 µg/ml for LOS and ATR, respectively. Detection limits were found to be 0.096 µg/ml and 0.030 µg/ml and quantitation limits were 0.291 µg/ml and 0.093 µg/ml for LOS and ATR, respectively. The proposed method was successfully applied to the analysis of both compounds in synthetic mixtures and in laboratory-prepared tablets. These results were in accordance with the results acquired using the comparison method, high-performance liquid chromatography.

Simultaneous estimation of amlodipine and atorvastatin by micelle-augmented first derivative synchronous spectrofluorimetry and multivariate analysis.

Five Selective, rapid and sensitive spectrofluorimetric methods were performed in this study for the simultaneous estimation of amlodipine besylate (AML) and atorvastatin (ATR) in their binary mixtures and combination polypills that are used for management of cardiovascular conditions. The first method depends on micelle-enhanced first derivative synchronous fluorimetric analysis (method I) and the other four methods are multivariate analysis techniques based on the use of factor-based calibration prediction methods comprising partial least squares (PLS), Principal Component Regression (PCR), genetic algorithm PLS (GA-PLS) and genetic algorithm PCR (GA-PCR). The synchronous fluorescence spectra of the solutions were measured at a constant wavelength difference; Δλ = 100 nm. The magnitudes of the peaks of the first derivative spectra (1D) were measured at 292 nm and 387 nm for ATR, and AML correspondingly. The multivariate models were constructed utilizing fifteen mixtures as a calibration set and ten mixtures as a validation set. The linearity of all the methods was in the concentration ranges of (0.1-4.0 µg mL-1, 0.4-10.0 µg mL-1) for AML and ATR, correspondingly. Statistical analysis revealed no significant difference between the proposed methods and the reference method. The validity of the proposed methods allows their suitability for quality control work. All the analysis settings were optimized and all the suggested procedures were applied productively for the determination of both drugs in synthetic mixtures, validation set, and combination polypills.

Development and full validation of an HPLC methodology to quantify atorvastatin and curcumin after their intranasal co-delivery to mice.

There is increasing interest in atorvastatin and curcumin owing to their potential anticancer activity. A new, accurate and sensitive HPLC method was developed, for the first time, to simultaneously quantify atorvastatin and curcumin in mouse plasma and brain, liver, lung and spleen tissues following protein precipitation sample preparation. The chromatographic separation was achieved in 13 min on a C18 column, at 35°C, using a mobile phase composed of acetonitrile-methanol-2% (v/v) acetic acid (37.5:2.5:60, v/v/v) at a flow rate of 1.0 mL/min. The detection of analytes and internal standard was carried out at 247, 425 and 250 nm, respectively. According to international guidelines, the method was shown to be selective, with lower limits of quantification ranging from 10 to 500 ng/mL for curcumin, and from 100 to 600 ng/mL for atorvastatin, linear over a wide concentration range (r2 ≥ 0.9971) and with acceptable accuracy (bias ± 12.29%) and precision (coefficient of variation ≤13.15%). The analytes were reproducibly recovered at a percentage >81.10% and demonstrated to be stable under various experimental conditions in all biological matrices. This method can be easily applied to in vivo biodistribution studies related to the intranasal administration of atorvastatin and curcumin, separately or simultaneously.

Access and concentrations of atorvastatin in the prostate in men with prostate cancer.

BACKGROUND: Statins have anticancer effects on prostate cancer both in vitro and in vivo. It is unclear whether this is due to systemic cholesterol-lowering or direct local growth inhibition in the prostate. It is also unclear whether statins can access the prostate; lipophilic statins could, in theory, pass lipid-enriched cell membranes by passive diffusion. However, statin concentrations in the human prostate have not been measured before. METHODS: The study population was based on a randomized clinical trial where 158 men with prostate cancer were randomized to use 80 mg atorvastatin (ATV) or placebo daily for a median of 27 days before radical prostatectomy. ATV and atorvastatin lactone (ATV-Lactone) concentrations in the plasma and in the prostate were measured with mass spectrometry in men randomized to the ATV arm. Linear trends between intraprostatic concentration and plasma concentration, body mass index, age, and duration of intervention were examined. The relative tissue concentrations of ATV and ATV-Lactone were calculated in prostatic tissue and plasma to evaluate drug homeostasis. Subgroup analyses were stratified by tumor and population characteristics. RESULTS: The analysis involved a total of 55 men. When limited to men whose tissue concentrations of ATV was measurable (n = 28, 50%), median ATV concentration was 212% higher in the tissue (median concentration 17.6 ng/g) compared to the plasma (median concentration 3.6 ng/mL). Also, ATV-L concentration was 590% higher in the tissue as compared to the plasma concentration. No statistically significant linear trends between the plasma and tissue concentrations were observed. When comparing the relative concentration of atorvastatin lactone over ATV, the concentrations were in balance in the plasma, In the prostate, however, the relative concentration of atorvastatin lactone was 57% lower compared to ATV (P = .009 for the difference between prostate tissue and plasma). No effect modification by tumor or population characteristics was observed. CONCLUSIONS: Measurable ATV concentrations in the prostate support ATV's ability to access the prostate from the circulation. ATV may accumulate in the prostate as intraprostatic concentrations are elevated compared to the plasma concentration.

[Application of the method of liquid chromato-mass spectrometry for determination of bisoprolol and atorvastatin.]

A technique has been developed for the quantitative determination of bisoprolol and atorvastatin in mixed saliva on a LCMS-8040 triple quadrupole liquid chromatographic mass spectrometer with ionization, separation and detection of samples, which allows determining the concentration in mixed saliva of bisoprolol with an accuracy of 93.7 to 98, 5% and atorvastatin from 95.6 to 98.3%.

Selective drug metabolite trace analysis by very high-volume injections and heartcut two-dimensional (2D)-ultrahigh performance liquid chromatography (UHPLC).

The application of two-dimensional liquid chromatography (2D-LC) is gradually growing also in the area of metabolite profiling and identification. The current contribution describes a heartcut 2D-UHPLC configuration that is applied in support of drug metabolism studies in development. The setup applies four LC columns: two analytical UHPLC columns to perform the first and second dimension separations, which are both preceded by a short HPLC column operated as trapping column. The first HPLC column allows a significant online preconcentration by large volume injection. The second short HPLC column is placed between the first and second dimension columns and enables the selection of orthogonal conditions in the second dimension independent of the first dimension making the heartcutting 2D approach more generic. The value of the setup was demonstrated with selective ultraviolet chromatograms obtained for the two major hydroxylated metabolites of atorvastatin separating them from a very high biological background, originating from an injection of 4 mL feces extract, by heartcut 2D-LC. In a second application, the main metabolite of imipramine was baseline separated from some minor metabolites that were co-eluting in the first dimension, allowing accurate and sensitive quantification. A quantification limit in the attogram/mL range was achieved thanks to the injection of 200 mL diluted urine, corresponding to 100 mL urine on column.

Determination of amlodipine and atorvastatin mixture by different spectrophotometric methods with or without regression equations.

Four new, simple, and reproducible spectrophotometric methods were developed and validated for the simultaneous determination of Amlodipine (AML) and Atorvastatin (AT) in bulk powder and pharmaceutical dosage form. The four methods include two progressive and two successive resolution techniques. The two progressive methods are Absorbance Subtraction (AS) and Amplitude Modulation (AM), while the two successive methods are Constant Value (CV) and Concentration Value. In the Concentration Value method, the concentration of the drugs is determined from the graphical representation without the use of regression equations. Linearity range for the two progressive methods was from 5 µg/mL-35 µg/mL while for the two successive methods was from 5 µg/mL-55 µg/mL. The four methods were validated according to the ICH guidelines and were found to be accurate, precise, and selective. The methods were also applied for determination of the mixture in the marketed pharmaceutical dosage form. Results obtained were compared with reported methods. Also, One-way ANOVA statistical test was done between all the proposed spectrophotometric methods where no significant differences were found.

Desenvolvimento de metodologia para avaliação do perfil de dissolução de comprimidos de atorvastatina cálcica 20 mg comercializados no Peru, Brasil e Bolívia / Development of a methodology to evaluate the dissolution profile of atorvastatin calcium tablets 20 mg marketed in Peru, Brazil and Bolivia

O presente estudo teve por finalidade desenvolver uma metodologia de dissolução discriminativa para avaliar comprimidos contendo diferentes polimorfos de atorvastatina cálcica (ATR). Este trabalho é conformado por quatro capítulos, no qual o primeiro apresenta uma breve revisão de literatura sobre as características dos polimorfos da ATR, abordando-se informações mais relevantes sobre o ATR em relação ao polimorfismo e sua influência na biodisponibilidade. No segundo capítulo, apresenta-se a importância da caracterização dos polimorfismos e suas implicações para a ATR. As amostras de ATR foram identificadas por difração raio X e análise térmica e, posteriormente, demonstrou-se as diferenças entre quatro amostras comercializadas no mercado brasileiro relacionadas ao hábito cristalino, tamanho de partícula e solubilidade. No terceiro capítulo, demonstra-se o desenvolvimento do método de dissolução discriminativo para comprimidos contendo duas formas polimórficas da ATR. Para tanto, avaliou-se a solubilidade destas pelo método do equilíbrio e determinou-se as condições experimentais mais adequadas para o ensaio de dissolução por intermédio de planejamento fatorial completo do tipo 23, sendo as variáveis independentes o meio de dissolução, a velocidade de agitação e as formas polimórficas (I e VIII). Os resultados obtidos foram tratados estatisticamente através da análise de variância, dos gráficos de Pareto e de superfície de resposta. Concluiu-se que a velocidade de agitação e o meio de dissolução impactam os resultados, afetando a dissolução das formulações com os polimorfos avaliados. Assim, as condições selecionadas foram: 750 mL de meio água a 65 rpm. Após o desenvolvimento do método, este foi comparado com o da Food and Drug Administration (FDA) para comprimidos de atorvastatina cálcica. Ao final dos ensaios, o método desenvolvido mostrou-se adequado para apontar diferenças entre os polimorfos da ATR. No quarto capítulo, o método desenvolvido foi utilizado para avaliar o perfil de dissolução de comprimidos comercializados em três países sul-americanos: Brasil, Peru e Bolívia. As porcentagens de fármaco dissolvidas e a Eficiência de Dissolução foram as variáveis estudadas e, posteriormente, tratadas estatisticamente através da análise de componentes principais, sendo possível comparar o perfil de dissolução de dessete formulações. Dessa forma, foi possível concluir que cinco formulações avaliadas (BR1, BR2 PE6, BR7 e BO3) possuíam a forma polimórfica VIII, enquanto duas formulações (BR5 e PE2) continham a forma polimórfica I. As demais, possivelmente, apresentam misturas ou outras formas polimórficas

This present study was aimed at developing a discriminative dissolution methodology to evaluate tablets containing different calcium atorvastatin (ATR) polymorphs. This paper consists of four chapters. The first chapter presents a brief literature review of the characteristics of ATR polymorphs, and addresses more relevant information about ATR in relation to polymorphism and its influence on bioavailability. The second chapter presents the importance of the characterization of polymorphs and their implications for ATR. The ATR samples were identified by X-ray diffraction and thermal analysis. Subsequently, the differences among the four samples marketed in the Brazilian market with relation to crystalline habit, particle size and solubility were demonstrated. The third chapter demonstrates the development of the discriminative dissolution method for tablets containing two polymorphic forms of ATR. For this, their solubilities were evaluated by the equilibrium method and the most suitable experimental conditions for the dissolution test were determined by means of complete factorial design of type 23, and the independent variables were the dissolution medium, the stirring speed and polymorphic forms (I and VIII). The results obtained were statistically treated through analysis of variance, Pareto and response surface graphs. It was concluded that the stirring speed and the dissolution medium influenced the results, affecting the dissolution of the formulations with the evaluated polymorphs. Thus, the selected condition was 750 mL of water at 65 rpm. Following the development of the method, it was compared with that of the Food and Drug Administration (FDA) for atorvastatin calcium tablets. At the end of the tests, the developed method was adequate to point out differences between the ATR polymorphs. In the fourth chapter, the developed method was used to evaluate the dissolution profile of tablets marketed in three South American countries: Brazil, Peru and Bolivia. Dissolved drug percentages and Dissolution Efficiency were the studied variables and statistically treated by principal component analysis. Through this method, it was possible to compare the dissolution profile of seventeen formulations. Thus, it was possible to conclude that five formulations evaluated (BR1, BR2, PE6, PE7 e BO3) had the polymorphic form VIII, while two formulations (BR5 e PE2) contained the polymorphic form I. The others possibly have mixtures or other forms polymorphic

Rapid quantitation of atorvastatin in process pharmaceutical powder sample using Raman spectroscopy and evaluation of parameters related to accuracy of analysis.

The purpose of this study was to determine the atorvastatin (ATV) content in process pharmaceutical powder sample using Raman spectroscopy. To establish the analysis method, the influence of the type of Raman measurements (back-scattering or transmission mode), preparation of calibration sample (simple admixing or granulation), sample pre-treatment (pelletization), and spectral pretreatment on the Raman spectra was investigated. The characteristic peak of the active compound was more distinctively detected in transmission Raman mode with a laser spot size of 4mm than in the back-scattering method. Preparation of calibration samples by wet granulation, identical to the actual manufacturing process, provided unchanged spectral patterns for the in process sample, with no changes and/or shifts in the spectrum. Pelletization before Raman analysis remarkably improved spectral reproducibility by decreasing the difference in density between the samples. Probabilistic quotient normalization led to accurate and consistent quantification of the ATV content in the calibration samples (standard error of cross validation: 1.21%). Moreover, the drug content in the granules obtained from five commercial batches were reliably quantified, with no statistical difference (p=0.09) with that obtained by HPLC assay. From these findings, we suggest that transmission Raman analysis may be a fast and non-invasive method for the quantification of ATV in actual manufacturing processes.

Simultaneous Determination of Acetylsalicylic Acid, Hydrochlorothiazide, Enalapril, and Atorvastatin in a Polypill-Based Quaternary Mixture by TLC.

A new chromatographic-densitometric method has been developed for the qualitative and quantitative determination of the active ingredients in a simulated mixture corresponding to the PolyIran polypill, composed of acetylsalicylic acid, hydrochlorothiazide (HCT), enalapril (ENA), and atorvastatin (ATR), whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials. Chromatographic separation was performed using TLC silica gel 60 plates with fluorescent indicator F254 as the stationary phase and a mixture of n-hexane-ethyl acetate-methanol-water-acetic acid (8.4 + 8 + 3 + 0.4 + 0.2, v/v/v/v/v) as the mobile phase. Densitometric measurements were carried out at λ = 210 nm when determining ENA and at λ = 265 nm in the case of the other drugs. Peaks of examined substances were well separated in the recorded chromatograms, enabling the evaluation of the results in terms of both qualitative and quantitative analysis. The method was specific for the analyzed components and was characterized by high sensitivity. The LOD was between 0.043 and 0.331 µg/spot, and LOQ was between 0.100 and 0.942 µg/spot. Recovery was in the range of 97.02-101.34%. The linearity range was broad and ranged from 0.600 to 6.000 µg/spot for acetylsalicylic acid, from 0.058 to 1.102 µg/spot for HCT, from 0.505 to 6.560 µg/spot for ENA, and from 0.100 to 1.000 µg/spot for ATR. The method was characterized by good precision, with RSD values that ranged from 0.10 to 2.26%.

Critical Review on the Analytical Techniques for the Determination of the Oldest Statin-Atorvastatin-in Bulk, Pharmaceutical Formulations and Biological Fluids.

Statins are a group of medicines that can help to lower the level of low-density lipoprotein (LDL) cholesterol "bad cholesterol" in the blood. Having a high level of LDL cholesterol is potentially dangerous, as it can lead to a hardening and narrowing of arteries (atherosclerosis) and cardiovascular disease (CVD), atorvastatin is one of the oldest member of the statin family and is used in the treatment of dyslipidemia and the prevention of CVD. Atorvastatin was first made in August 1985 and from 1996 to 2012 under the trade name Lipitor, atorvastatin became the world's best-selling drug. Numerous analytical methodologies are available for the quantification of atorvastatin and its content in pharmaceutical preparations and in biological fluids.

Combined Liquid Chromatography-Infrared Ion Spectroscopy for Identification of Regioisomeric Drug Metabolites.

High-performance liquid chromatography was used in combination with infrared ion spectroscopy for the identification of positional isomers of hydroxy-atorvastatins, the primary metabolites of the drug atorvastatin. The results demonstrate the direct applicability of infrared ion spectroscopy in the field of drug metabolism and, more generally, its promising role in state-of-the-art analytical laboratories for the identification of small molecules buried in complex mixtures. In combination with chromatographic separation, infrared spectroscopy of mass-selected ions provides a promising new route for the identification of the molecular structures of unknown m/z peaks in a mass spectrum. We demonstrate that currently existing experimental protocols allow the measurement of an IR spectrum from less than 10 ng of sample obtained in a collected HPLC fraction.

Spectrophotometric method for simultaneous determination of valsartan and substances from the group of statins in binary mixtures.

Applicability of derivative spectrophotometry for the determination of valsartan in the presence of a substance from the group of statins was checked. The obtained results indicate that the proposed method may be effective by using appropriate derivatives: for valsartan and fluvastatin - D1, D2 and D3, for valsartan and pravastatin - D1 and D3, for valsartan and atorvastatin - D2 and D3. The method was characterized by high sensitivity and accuracy. Linearity was maintained in the following ranges: 9.28-32.48 mg mL-1 for valsartan, 8.16-28.56 mg mL-1 f or fluvastatin, 14.40-39.90 mg mL-1 for atorvastatin and 9.60-48.00 mg mL-1 for pravastatin. Determination coefficients were in the range of 0.989-0.999 depending on the analyte and the order of derivative. The precision of the method was high with RSD from 0.1 to 2.5 % and recovery of individual components was within the range of 100 ± 5 %. The developed method was successfully applied to the determination of valsartan combined with fluvastatin, atorvastatin and pravastatin in laboratory prepared mixtures and in pharmaceutical preparations.

Development and validation of HPLC and CE methods for simultaneous determination of amlodipine and atorvastatin in the presence of their acidic degradation products in tablets.

Two methods were developed for separation and quantitation of amlodipine (AML) and atorvastatin (ATV) in the presence of their acidic degradation products. The first method was a simple isocratic RP-HPLC method while the second was capillary electrophoresis (CE). Degradation products were obtained by acidic hydrolysis of the two drugs and their structures were elucidated for the first time by IR and MS spectra. Degradation products did not interfere with the determination of either drug and the assays were therefore stability-indicating. The linearity of the proposed methods was established over the ranges 1-50 µg mL-1 for AML and ATV in the HPLC method and in the range of 3-50 and 4-50 µg mL-1 for AML and ATV, respectively, in the CE method. The proposed methods were validated according to ICH guidelines. The methods were successfully applied to estimation of AML and ATV in combined tablets.

Application of carbon nanotubes-ionic liquid hybrid in a sensitive atorvastatin ion-selective electrode.

Atorvastatin (ATR) was determined by a potentiometric method. The ion-pair of ATR and cetyltrimethylammonium bromide (CTAB) was used as a suitable ionophore. A graphite paste electrode was modified with ATR-CTAB ion-pair, multiwalled carbon nanotubes (MWCNTs), and an ionic liquid, 1-butyl-3-mtehyl-imidazolium hexafluorophosphate (BMIMPF6). The amounts of electrode ingredients were optimized (graphite powder: paraffin oil: ATR-CTAB: MWCNTs: BMIMPF6 (58:26:5:8:3 w/w%). Surface characterization was done by using scanning electron microscopy. The potential measurements were recorded at optimized pH by using acetate buffer solution (0.1molL(-1), pH5.5). At the above experimental conditions, calibration curve (E vs. log [ATR]) was linear (R(2)=0.9977) in the concentration range of 1.0×10(-9)-1.0×10(-3)molL(-1) (0.0012-1209mgL(-1)) of ATR with a Nernstian slope of 58.14±0.2mV decade(-1), and detection limit of 1.0×10(-9)molL(-1) (0.0013mgL(-1)). After each injection of ATR to the buffer solution, the potential was stabilized in a very short time (average response time~6s) at 25°C. The modified graphite paste electrode had a long lifetime (>4months). Recovery of the spiked drug to blood serum samples (95.3-98.2%) revealed the reliability of electrode response to ATR. Blood serum samples from consumers were analyzed by the proposed method; the results were comparable with those from HPLC standard method. The potentiometric analysis of ATR tablets by the proposed electrode resulted in a relative error of 0.8% and 1.5% for 20 and 40mg per tablets, respectively. Finally, the electrode was used in potentiometric titration of ATR (1.0×10(-3)molL(-1)) by CTAB (1.0×10(-3)molL(-1)). Excellent accuracy (≈100%) was obtained from the volume of the titrant at the endpoint.