Binder-free and efficient voltammetric sensor based on Zn-Ca2CuO3 nanoparticles for simultaneous determination of amlodipine, acetaminophen, and ascorbic acid in hypertension patients.

Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting molecules acetaminophen (AP) and ascorbic acid (AA) are recommended for hypertension control and prevention. Considering their therapeutic importance and potential side effects due to over dosage, we have fabricated a sensor for individual and simultaneous determination of AA, AP, and AM in pharmaceuticals and human urine using novel Zn-doped Ca2CuO3 nanoparticles modified glassy carbon electrode (GCE). Optimally doped Ca2CuO3 (2.5 wt% Zn at Cu site) enhanced the detection of target molecules over much wider concentration ranges of 50 to 3130 µM for AA, 0.25 to 417 µM for AP, and 0.8 to 354 µM for AM with the corresponding lowest detection limits of 14 µM, 0.05 µM, and 0.07 µM, respectively. Furthermore, the Zn-Ca2CuO3/GCE exhibited excellent selectivity and high sensitivity even in the presence of several potential interfering agents. The usefulness of the developed electrode was tested using an amlodipine besylate tablet and urine samples of seven hypertension patients under medication. The results confirmed the presence of a significant amount of AP and AM in six patients' urine samples indicating that the personalized medication is essential and the quantum of medication need to be fixed by knowing the excess medicines excreted through urine. Thus, the Zn-Ca2CuO3/GCE with a high recovery percentage and good sensitivity shall be useful in the pharmaceutical and biomedical sectors.

Microchip isotachophoresis for green and sustainable pharmaceutical quality control: Method validation and application to complex pharmaceutical formulations.

Universal microchip isotachophoresis (µITP) methods were developed for the determination of cationic and anionic macrocomponents (active pharmaceutical ingredients and counterions) in cardiovascular drugs marketed in salt form, amlodipine besylate and perindopril erbumine. The developed methods are characterized by low reagent and sample consumption, waste production and energy consumption, require only minimal sample preparation and provide fast analysis. The greenness of the proposed methods was assessed using AGREE. An internal standard addition was used to improve the quantitative parameters of µITP. The proposed methods were validated according to the ICH guideline. Linearity, precision, accuracy and specificity were evaluated for each of the studied analytes and all set validation criteria were met. Good linearity was observed in the presence of matrix and in the absence of matrix, with a correlation coefficient of at least 0.9993. The developed methods allowed precise and accurate determination of the studied analytes, the RSD of the quantitative and qualitative parameters were less than 1.5% and the recoveries ranged from 98 to 102%. The developed µITP methods were successfully applied to the determination of cationic and anionic macrocomponents in six commercially available pharmaceutical formulations.

Sensitive surface plasmon resonance biosensor by optimized carboxylate functionalized carbon nanotubes/chitosan for amlodipine detecting.

The adoption of biophotonic sensing technologies holds significant promise for application in health care and biomedical industries in all aspects of human life. Then, this piece of writing employs the powerful effective medium theory and FDTD simulation to anticipate the most favorable state and plasmonic attributes of a magnificent nanocomposite, comprising carboxylate functionalized carbon nanotubes and chitosan (CS). Furthermore, it thoroughly explores the exhibited surface plasmon resonance behaviors of this composite versus the quantity of CS variation. Subsequently, enlightening simulations are conducted on the nanocomposite with a delicate layer and a modified golden structure integrating as a composite. The intricate simulations eventually unveil an optimal combination to pave the way for crafting an exceptional specific biosensor that far surpasses its counterpart as a mere Au thin layer in terms of excellence. The proposed biosensor demonstrated linear behavior across a wide range from 0.01 µM to 150 µM and achieved a detection limit of 10 nM, with a sensitivity of 134◦RIU-1.

UV imaging for the rapid at-line content determination of different colourless APIs in their tablets with artificial neural networks.

This paper presents a novel high-resolution and rapid (50 ms) UV imaging system, which was used for at-line, non-destructive API content determination of tablets. For the experiments, amlodipine and valsartan were selected as two colourless APIs with different UV induced fluorescent properties according to the measured solid fluorescent spectra. Images were captured with a LED-based UV illumination (385-395 nm) of tablets containing amlodipine or valsartan and common tableting excipients. Blue or green colour components from the RGB colour space were extracted from the images and used as an input dataset to execute API content prediction with artificial neural networks. The traditional destructive, solution-based transmission UV measurement was applied as reference method. After the optimization of the number of hidden layer neurons it was found that the relative error of the content prediction was 4.41 % and 3.98 % in the case of amlodipine and valsartan containing tablets respectively. The results open the possibility to use the proposed UV imaging-based system as a rapid, in-line tool for 100 % API content screening in order to greatly improve pharmaceutical quality control and process understanding.

Utility of Cilefa Pink B, a foodstuff dye as a fluoro-substrate in the devising of the first facile green Molecular-mass-Related Fluorescence Sensor for quantifying amlodipine in batched material and dosage forms; content uniformity evaluation.

This study introduces the first and unique Molecular-mass-Related Fluorescence Sensor as the first fluorimetric strategy for determining amlodipine. An environmentally friendly, single-step, and direct spectrofluorimetric approach was utilized to evaluate the analyte. In an acidic setting, combining the amlodipine medication and the fluorescent dye Cilefa Pink B generated an instantaneous ultra-fluorescent product. An increase in dye response after adding amlodipine was proportional to the molecular weight of the generated complex, as measured at 329 nm. was the idea ofthe applied fluorimetric analysis. The complexing process increased the molecular mass from 879.86 to 1288.739 g mol-1. The medication's range of 0.050-1.00 µg mL-1 is directly correlated with this molecular massenlargement. The ideal settings for the changeable parameters of the system were established through an analysis of the response of the amlodipine-Cilefa Pink B system. Furthermore, the developed sensor complied with ICH (International Council for Harmonization) standards. The sensitivity limits were 0.0139 µg mL-1 (for the detection limit, LOD) and 0.042 µg mL-1 (for the quantification limit, LOQ). Additionally, this method effectively recovered the drug in its original and therapeutic dosage forms. Finally, the proposed process's environmental impact was also assessed through different modern greenness evaluation tools.

Simultaneous Estimation of Telmisartan, Chlorthalidone, Amlodipine Besylate and Atorvastatin by RP-HPLC Method for Synchronous Assay of Multiple FDC Products Using Analytical FMCEA-Based AQbD Approach.

Numerous reversed-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) techniques have been published for the estimation of fixed-dose combinations (FDCs) of telmisartan (TEL). No published literature has been reported to date which described the synchronous estimation of FDCs of TEL using a single chromatography condition. Hence, the RP-HPLC method has been developed and validated for synchronous analysis of FDCs of TEL using an enhanced analytical quality by design (AQbD) approach to save time, cost and solvent for analysis. The implementation of AQbD was initiated with the identification of failure modes (FMs) using the Ishikawa diagram, and their critical effect analysis was carried out by risk priority number ranking and filtering method. The identified critical FMs were optimized by design of experiments-based response surface modeling using the Box-Behnken design. The method operable design region was navigated and control strategy was framed to mitigate the risk of critical FM. The RP-HPLC method was developed using Shim-Pack octadecyl silane C18 column and acetonitrile: 1.0%v/v triethylamine (pH 6.5 adjusted using perchloric acid; 42:58, %v/v). The developed method was found to be validated as per the International Council For Harmonization Q2 (R1) guideline. The method was applied for the synchronous assay of seven different FDCs of TEL and assay results were found in good compliance with the respective labeled claim.

Analysis of Fixed-Dose Combination of Three Antihypertensive Drugs by a Green and Quality by Design Approach.

This paper presents the result of a combined employment of Analytical Quality-by-Design and Green Analytical Chemistry principles for the development of a robust high-performance liquid chromatography method for simultaneous determination of fixed-dose combination of three drugs, perindopril tert-butylamine, amlodipine besylate and indapamide. Optimum conditions were achieved on ZORBAX Eclipse XDB-C18 column (150 mm × 4.6 mm, 5 µm particle size), the mobile phase comprising acetonitrile and phosphate buffer (30 mM, pH 2.7) in the ratio 34:66 (v/v), the flow rate of 1 mL min-1, injection volume of 10 µL and UV detection at 210 nm. By assigning the design space from the overlay plot, the regions within which the robustness of the method is achieved were defined and confirmed by Dong's algorithm calculations. The proposed method was validated and shown to be applicable for the determination of the three drugs in commercially available tablets. In addition, the impact of the method on the environment was assessed through four different analytical tools: National Environmental Methods Index, Analytical Eco-Scale, Green Analytical Procedure Index and Assessment of Green Profile. The proposed method was determined to be greener, with minimal impact on the environment with regard to waste production, energy consumption and use of hazardous chemicals.

In Vitro Dissolution Profile of Antihypertensive Mixture: Comparison Between Multivariate Methods and Statistical and Graphical Representation of Different Univariate Spectrophotometric Data.

BACKGROUND: Triplixam® is a new antihypertensive drug combination consisting of perindopril, amlodipine, and indapamide, which have a synergistic mechanism of action in combination with each other. OBJECTIVE: Comparative study of different spectrophotometric approaches used for the simultaneous determination of perindopril, indapamide, and amlodipine in bulk powder and in dosage form Triplixam. METHOD: The methods include univariate and multivariate spectrophotometric methods depending on either mathematical calculation or graphical representation of data. For the univariate methods: perindopril was resolved from other components using constant multiplication followed by spectrum subtraction resolution technique, and then two base point, AUC, constant value, and concentration value (CNV) methods were applied. For both amlodipine and indapamide: constant multiplication resolution technique was used, and then constant value and CNV methods were applied. CNV depends on graphical representation of data rather than statistical data. PLS and PCR chemometric assisted spectrophotometric techniques were also applied. The proposed methods are considered a green alternative to the reported methods as the greenness of the proposed methods was evaluated qualitatively and quantitatively by four green analytical evaluation tools. RESULTS: The methods were applied for the analysis of the mixture in the pharmaceutical dosage form Triplixam and in vitro release at intestinal pH (7.4) using a USP dissolution tester. CONCLUSIONS: The proposed green analytical methods are considered to be greener than the reported methods and simpler, so they could be used as an alternative for routine analysis of the mixture in quality control laboratories for the reason of their accurate results beside minimum manipulation steps that reduced the error and time required of the analysis with no harmful effect on analyst health as well as the environment. HIGHLIGHTS: The study was the first in vitro dissolution profiling of perindopril, amlodipine, and indapamide. The developed methods were excellent green methods without compromising the analytical criteria.

Carboxymethyl-ß-cyclodextrin and histidine-zeolitic imidazolate framework-8 used for enantioseparation of three basic drugs in open-tubular capillary electrochromatography.

Metal organic frameworks (MOFs) have drawn broad attention as a novel stationary phase due to their highly porous structure, modifiable pores, large specific surface areas, and satisfactory stability. In this paper, histidine-zeolitic imidazolate framework-8 (His-ZIF-8) synthesized at room temperature was physically coated to the internal surface of the capillary column and the carboxymethyl-ß-cyclodextrin (CM-ß-CD) as the chiral selector was chemically bonded to the His-ZIF-8@capillary column. The prepared CM-ß-CD@His-ZIF-8@capillary column was used for the enantioseparation of amlodipine, propranolol, and atenolol in capillary electrochromatography. In contrast to the CM-ß-CD@capillary column without His-ZIF-8, the CM-ß-CD@His-ZIF-8@capillary column reveals significantly improved enantiodiscrimination performance for amlodipine (Rs : 0 → 2.29), propranolol (Rs : 0 → 1.69), and atenolol (Rs : 0 → 0.79). His-ZIF-8 concentration, buffer pH, buffer concentration, and the proportion of organic modifier were evaluated in detail with enantiomerically separating chiral molecules. The repeatability of intraday, day-to-day, and column-to-column have been discussed; the result was preferable, and the relative standard deviation (RSD) of separation parameters was <6.7%.

Different Approaches in Manipulating Ratio Spectra for Analyzing Amlodipine Besylate and Irbesartan Combination.

BACKGROUND: Hypertension is a key risk factor for ischemic heart disease and atherosclerosis. Most patients require a combination of antihypertensive medications to accomplish their therapeutic goals. Antihypertensive medicines such as calcium channel blockers and angiotensin receptor blockers are indicated for patients whose high blood pressure cannot be controlled with monotherapy. The combination of amlodipine besylate (AML) with irbesartan (IRB) is an example of this synergistic activity in lowering blood pressure. OBJECTIVE: In this regard, the goal of the research is to develop sensitive spectrophotometric methods for the simultaneous determination of amlodipine besylate and irbesartan. METHODS: Three simple ratio spectra-manipulating spectrophotometric methods namely, ratio difference, mean centering of ratio spectra, and derivative ratio, were developed for the simultaneous assay of the cited mixture. RESULTS: Linear correlations were attained over the concentration range of 1-35 µg/mL and 2-35 µg/mL for amlodipine besylate and irbesartan, respectively. The methods were validated according to the International Conference on Harmonization guidelines with good results. CONCLUSION: The methods developed were successfully applied for the assay of the cited drugs in their marketed formulation. They could be efficiently used for routine analysis of the mentioned drugs in QC laboratories. HIGHLIGHTS: The proposed approaches do not require expensive solvents or complex instruments. They could be used in routine laboratory tests where time and cost are crucial.

Simultaneous determination of hydrochlorothiazide, amlodipine, and telmisartan with spectrophotometric and HPLC green chemistry applications.

For the quantifiable amounts of Telmisartan (TLM) and Hydrochlorothiazide (HYD) in the presence of Amlodipine (AML) in a ternary mixture of synthetic laboratory mixture, a novel, sensitive, quick, and practical reversed-phase high-performance liquid chromatography (RP-HPLC) method was given. In order to separate, a Waters Spherisorb ODS-2 C18 column was used. For HYD, TLM, and AML, these techniques were viable over linearity ranges of 4-12 µg/mL, 4-25 µg/mL, and 5-40 µg/mL, respectively. The mobile phase system was acetonitrile:methanol: phosphate buffer at pH 2.5 (65:5:30 v/v/v), and the flow rate was 1.5 mL/min. Novel spectrophotometric methods were applied for active substances to determine simultaneously. The first method is absorptivity centering using factorized spectrum, and the second method is dual amplitude difference coupled with absorbance subtraction. These approaches have been effectively applied to bulk, laboratory synthetic mixtures to employ active components quantitatively. Correlation coefficients were found to be higher than 0.99 and the limit of detection values lower than 0.49 µg/mL in both spectrophotometric methods. The methodologies were validated following ICH recommendations. In the developed HPLC method, the limit of detection values was found to be 0.01 µg/mL for HYD and 0.02 µg/mL for AML and TLM. The correlation coefficients for the HPLC method were found to be 0.9971 for HYD, 0.9990 for AML, and 0.9983 for TLM. The suggested HPLC technique is a simple, effective, sensitive, environmentally friendly, and time-saving approach for determining TLM and HYD in the presence of AML.

Eco-friendly spectrophotometric evaluation of triple-combination therapies in the treatment strategy of patients suffering from hypertension during coronavirus pandemic - Spectralprint recognition study.

Recent studies have reported that using certain antihypertensive therapies such as angiotensin II receptor blockers (ARBs) and calcium channel blocker (CCBs) is associated with reduction of fatal outcomes and improving clinical characteristics of patients suffering from hypertension during coronavirus pandemic. Thus, in the current work an effective, innovative and eco-friendly spectrophotometric manner namely, parent spectrum extraction (PSE)was established for evaluation of recommended triple antihypertensive combination therapies incorporate valsartan (VAL) as ARBs, amlodipine besylate as CCBs (AML) and hydrochlorothiazide (HCT)as diuretic into single-pill in challengeable ratio. PSE manner composed of two complementary steps, auxiliary resolution coupled with data analysis resolution(DAR)and it is characterized by resolving the spectral bands of the drugs and extraction of their discrete parent spectra (D0); accordingly, enabling determination of each analyte at its λmax. Auxiliary resolution of AML in triple mixture was applied to decrease complexity of overlapped spectra via constant multiplication (CM) followed by spectrum subtraction (SS) to obtain resolved mixture of VAL and HCT while data analysis resolution (DAR) of this binary mixture was applied via one of three novel methods namely, absorbance extraction (AE), peak-amplitude extraction (PE) and ratio extraction (RE) along with SS method. The proposed methods had analyzed VAL, AML and HCT in the range of 4.0-44.0 µg/mL, 4.0-40.0 µg/mL and 2.0-24.0 µg/mL, respectively with an excellent correlation coefficient (r ≥ 0.9999). Further, the proposed methods in PSR manner were validated as stated by ICH guidelines and it was found that accuracy and precision results are within the acceptable limit. The suggested procedures were effectively utilized for the concurrent quantification of VAL, AML and HCT in synthetic mixtures and tablets. The greenness of the proposed spectrophotometric methods was evaluated by National Environmental Methods Index (NEMI), the Analytical Eco-Scale, the Green Analytical Procedure Index (GAPI) and Analytical greenness metric (AGREE) where the four tools affirmed the eco-friendly nature of the proposed methods. A comparison between the outcomes of the studied methods with the official and reported ones was performed and no statistical difference was arisen between the methods regarding to accuracy and precision.The achieved results along with the simplicity, affordability and low-cost of the proposed methods recommended their appropriateness for the regular quality control examination and analysis of pure materials and pharmaceutical formulations as well as their applicability for the spectralprint recognition of the studied drugs.

Zeolitic imidazolate framework-67-modified open-tubular column with cyclodextrin for enantioseparation in capillary electrochromatography.

The histidine-modified zeolitic imidazolate framework [His-ZIF-67] was prepared with the histidine, 2-methylimidazole, and Co2+ under ambient temperature. His-ZIF-67 was bonded via a glycidyl methacrylate copolymer to the internal surface of capillary and then functionalized with the NH2 -ß-cyclodextrin (NH2 -ß-CD). The materials were characterized by field emission scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, N2 adsorption-desorption isotherm, X-ray diffraction, and X-ray photoelectron spectroscopy. In comparison with the NH2 -ß-CD@capillary, the NH2 -ß-CD@His-ZIF-67@capillary-coated column shows significantly enhanced resolution for chiral molecules. The NH2 -ß-CD@His-ZIF-67@capillary column achieved the baseline separation of amlodipine and metoprolol (the resolution of amlodipine: 1.70; metoprolol: 1.50) and the partial separation of atenolol and propranolol (the resolution of atenolol: 1.03; propranolol: 0.60). These were attributed to the histidine modification and the features of ZIF-67, including an excellent surface area and the abundant porosity. The pH and proportion of organic modifier in the buffer were crucial for enantioseparation performance and were evaluated in detail. The fabricated NH2 -ß-CD@His-ZIF-67@capillary-coated column showed good stability and repeatability (relative standard deviation <6.3%). The molecular modeling with AutoDock and grand canonical ensemble was carried out to evaluate the interactions between chiral stationary phase and racemic drugs.

The power of High Impact Amplitude Manipulation (HIAM) technique for extracting the basic spectra of two Fixed-dose combinations (FDC) -Spectrophotometric purity analysis via spectral contrast angle.

HIAM technique allows the extraction of the original constant signal of each single component out of interference signals of a mixture and further transformed into basic spectrum (D0). It includes the methods: ratio subtraction coupled with unified constant subtraction (RS-UCS), constant center (CC) and constant extraction (CE). The technique was introduced for the analysis of two pharmaceutical formulations used to treat cardiovascular diseases. The formulations are binary combinations of Amlodipine (AML) with either Atorvastatin (ATR) or Candesartan (CND) which shows interefernce absorbance signals. The technique was valid over the linearity range of (5.0-35.0 µg/ml) for AML, ATR and CND with recovery percentage 100.40 ± 1.88 , 100.00 ± 0.86 and 99.83 ± 1.07, respectively . The extracted signals were tested for its purity by spectral contrast angle (cos θ) to illustrate the efficency of the HIAM technique where cos θ values ranges from (0.9902 to 0.9986). The presented technique was fully validated regarding ICH guidelines and were statistically compared using one-way ANOVA at 95% confidence.

Quantitative Analysis of Two Pharmaceutical Combinations Containing Amlodipine with Either Bisoprolol or Candesartan Using Different UV Spectrophotometric Methods.

BACKGROUND: Two fixed-dose combination tablets of amlodipine (AML) with bisoprolol (BIS) and amlodipine with candesartan (CAN) were recently approved for the treatment of hypertension. OBJECTIVE: Three UV spectrophotometric analytical methods were developed for the estimation of the above drugs in their combination mixtures. METHODS: For the AML and BIS mixture, AML was quantified directly by a zero-order spectrophotometric method at 360 nm without interference from BIS, whereas BIS was quantified by the ratio difference (RD) spectrophotometric method by calculating the difference between the amplitude values of the ratio spectra at 226 and 215 nm. For the AML and CAN mixture, AML was quantified directly by a zero-order spectrophotometric method at 360 nm without interference from CAN, whereas CAN was quantified by the first derivative of ratio spectra method by measuring the amplitude values of the derived spectra at 259 nm.BIS). RESULTS: The proposed methods were successfully applied for quantitative analysis of AML with BIS and AML with CAN in their synthetic laboratory-prepared mixtures and pharmaceutical tablets with acceptable results in terms of accuracy and precision. CONCLUSION AND HIGHLIGHTS: Simple, accurate, and environmentally friendly spectrophotometric methods were described for selective determination of the investigated drugs in their fixed-dose combinations.

Development and validation of a stability-indicating UPLC method for the determination of olmesartan medoxomil, amlodipine and hydrochlorothiazide degradation impurities in their triple-combination dosage form using factorial design of experiments.

The current work describes the development and validation of a stability-indicating UPLC method for the determination of olmesaratan medoxomil (OLM), amlodipine besylate (AMB), hydrochlorothiazide (HCT) and their degradation products in the triple-combination tablet dosage form. The separation was achieved using a Zorbax Eclipse plus C8 RRHD (100 mm × 3.0 mm), 1.8 µm column with gradient elution of mobile phase A containing 0.02 m of sodium phosphate buffer (pH 3.35) and mobile phase B as acetonitrile and water (90:10, v/v). The detector signal was monitored at UV 250 nm. Analytical performance of the optimized UPLC method was validated as per International Conference on Harmonization guidelines. The linearity ranges for OLM, AMB and HCT were 0.59-240, 0.30-60 and 0.37-150 µg/ml, respectively, with correlation coefficients >0.999. The dosage form was subjected to forced-degradation conditions of neutral, acidic and alkaline hydrolysis, oxidation and thermal and photodegradation. The method was proved to be stability indicating by demonstrating the specificity of the drugs from degradation products. The robustness of the method was evaluated through a two-level, three-factorial design with a multivariate approach. Statistical data analysis with best model fit P-value < 0.05 from an ANOVA test indicated that the influence of individual factors is relatively higher than the interaction effects. The method is useful for the analysis of drug products.

High performance liquid chromatographic assay of amlodipine, valsartan and hydrochlorothiazide simultaneously and its application to pharmaceuticals, urine and plasma analysis.

A Simple, Specific, Precise, Accurate, Linear, Rugged, Robust High Performance Liquid Chromatographic method of analysis for simultaneous determination of assay of Amlodipine, Valsartan and Hydrochlorothiazide drugs in the pharmaceuticals tablet formulations using Pioglitazone as a common internal standard was developed and validated. The assay was accomplished using a mixture of acetonitrile & methanol in the volume ratio of 20:80 v/v (mobile phase B) and Ammonium acetate buffer (Mobile phase A) in gradient flow as mobile phase on an Hibar RP-18e, 250 × 4.6 mm, 5µ as chromatographic column at a flow rate of 1.300 mLmin-1, injection volume 10 µL and at a wavelength 235 nm with UV detector. Linearity of the analytical method was evaluated at a concentration range of 2.5-45.3 µg/ml for Amlodipine, 32.0-720.1 µg/ml for valsartan and 5.0-112.6 µg/ml for Hydrochlorothiazide respectively with Correlation coefficient (r) value more than 0.9997. The limit of detection (LOD) for Amlodipine, Valsartan and Hydrochlorothiazide was found to be 1.1 µg/ml, 8.0 µg/ml & 1.0 µg/ml respectively. Specificity, Method Precision, System Precision, Ruggedness, Robustness, Recovery, Stability of analytical solution, Filter paper selection study, Stress testing (Force Degradation) at various conditions were performed as per the ICH (Q2) recommendations. The chromatographic method may also be applied for simultaneous estimation of analytes in plasma and urine.

A Drug Content, Stability Analysis, and Qualitative Assessment of Pharmacists' Opinions of Two Exemplar Extemporaneous Formulations.

Despite a decline in the number of active pharmaceutical ingredients prepared extemporaneously using proprietary products, there remains a need for such products in the community (for example, liquid medicines for paediatrics which may be otherwise commercially unavailable). A lack of experience and quality assurance systems may have diminished pharmacist's confidence in the extemporaneous preparation process; therefore, pharmacists were asked to prepare two proprietary products, omeprazole and amlodipine. The resulting products were characterised in terms of variability in drug quantity, stability, particle size and antimicrobial properties. Furthermore, a self-administered questionnaire was used to assess 10 pharmacists' opinions on the perceived complexity of the extemporaneous compounding process and their overall confidence in the final extemporaneously compounded products. Drug content studies revealed that 88.5% and 98.0% of the desired drug content was obtained for omeprazole and amlodipine, respectively. Antimicrobial properties were maintained for both drugs, however variability in particle size, particularly for amlodipine, was evident between formulations. While pharmacists who partook in the study had some or high confidence in the final products, they reported difficulty formulating the suspensions. Findings from this study provide insight into pharmacists' views on two extemporaneously prepared products and highlight the variability obtained in preparations prepared by different pharmacists.

A fast and green reversed-phase HPLC method with fluorescence detection for simultaneous determination of amlodipine and celecoxib in their newly approved fixed-dose combination tablets.

A fast, green, sensitive, and accurate analytical method using high-performance liquid chromatography couple with fluorescence detection was established and validated for the simultaneous determination of amlodipine besylate and celecoxib in their recently approved fixed-dose combination tablets (1:20). Separation of the two drugs was achieved on C18 reversed-phase column (Thermo ODS Hypersil, 4.6 × 250 mm, particle size 5 µm) using acetonitrile:potassium phosphate buffer (50 mM; pH 5.5, 60:40 v/v) as a mobile phase at 40°C, which eluted at a rate of 1 mL/min. Detection was carried out with excitation and emission wavelengths of 360 and 446 nm for amlodipine and 265 and 359 nm for celecoxib, respectively. The method was linear over a concentration range of 0.05-2 and 0.05-10 µg/mL and limit of detection reached to 0.017 and 0.0167 µg/mL for amlodipine and celecoxib, respectively. The developed method was successfully applied to assess the cited drugs in their newly FDA approved fixed-dose combination tablet dosage form. Furthermore, the method was found to be sensitive and eco-friendly green alternative to the reported methods as it was evaluated according to the green analytical procedure index tool guidelines and analytical Eco-Scale.

Use of Gamithromycin as a Chiral Selector in Capillary Electrophoresis.

In this short communication, we report the use of a second-generation macrolide antibiotic, gamithromycin (Gam), as a novel chiral selector for enantioseparation in capillary electrophoresis (CE). A preliminary analysis of the experiment results shows that Gam is especially suitable for the separation of chiral primary amines. Factors influencing enantioseparations were systematically investigated including the composition of the background electrolyte (BGE), concentration of Gam, the type and proportion of organic solvents, applied voltage, etc. In particular, N-Methylformamide (NMF) was successfully used as a non-aqueous solvent for Gam, and shown to be extremely effective for the separation of primaquine (PMQ) and 1-aminoindan (AMI) when used alone or mixed with other commonly used non-aqueous solvents (e.g. methanol). To our knowledge this was also the first application of NMF as a non-aqueous solvent for antibiotic chiral selectors in CE. The best separations were obtained with 100 mM Tris, 125 mM H3BO3 and 80 mM Gam in methanol/NMF (25:75) solvent for PMQ and AMI, or 80-100 mM Gam in methanol for the other model analytes. Among the analytes, the resolution (Rs) of amlodipine (AML) reached up to 15.65, which is to our knowledge the highest value ever reported in CE studies for this compound (except for using molecularly imprinted polymers technique).