Quality Control Of Pharmaceutical Formulations Research Articles

Determination of Aminoglycosides by Ion-Pair Liquid Chromatography with UV Detection: Application to Pharmaceutical Formulations and Human Serum Samples.

Aminoglycosides (AGs) represent a prominent class of antibiotics widely employed for the treatment of various bacterial infections. Their widespread use has led to the emergence of antibiotic-resistant strains of bacteria, highlighting the need for analytical methods that allow the simple and reliable determination of these drugs in pharmaceutical formulations and biological samples. In this study, a simple, robust and easy-to-use analytical method for the simultaneous determination of five common aminoglycosides was developed with the aim to be widely applicable in routine laboratories. With this purpose, different approaches based on liquid chromatography with direct UV spectrophotometric detection methods were investigated: on the one hand, the use of stationary phases based on hydrophilic interactions (HILIC); on the other hand, the use of reversed-phases in the presence of an ion-pairing reagent (IP-LC). The results obtained by HILIC did not allow for an effective separation of aminoglycosides suitable for subsequent spectrophotometric UV detection. However, the use of IP-LC with a C18 stationary phase and a mobile phase based on tetraborate buffer at pH 9.0 in the presence of octanesulfonate, as an ion-pair reagent, provided adequate separation for all five aminoglycosides while facilitating the use of UV spectrophotometric detection. The method thus developed, IP-LC-UV, was optimized and applied to the quality control of pharmaceutical formulations with two or more aminoglycosides. Furthermore, it is demonstrated here that this methodology is also suitable for more complex matrices, such as serum, which expands its field of application to therapeutic drug monitoring, which is crucial for aminoglycosides, with a therapeutic index ca. 50%.

ПРИМЕНЕНИЕ СОРБЕНТА ДЛЯ ТВЕРДОФАЗНОЙ ЭКСТРАКЦИИ НА ОСНОВЕ ГИПРОМЕЛЛОЗЫ ДЛЯ КОЛИЧЕСТВЕННОГО ОПРЕДЕЛЕНИЯ КИСЛОТЫ САЛИЦИЛОВОЙ В КОМБИНИРОВАННЫХ ЛЕКАРСТВЕННЫХ ПРЕПАРАТАХ

Introduction. In quality control of pharmaceutical formulations, there are methodological approaches based on the preliminary separation of sample components and approaches without preliminary separation. The use of solid-phase extraction (SPE) allows to separate analytes during sample preparation, with the separation selectivity determining the analysis selectivity as a whole. Currently, sorbents that provide selectivity in interaction with the analyte are of interest. Various derivatives of cellulose are used to obtain selective sorbents: ethylcellulose, hydroxypropylmethylcellulose (hypromellose), carboxymethylcellulose, etc. On the pharmaceutical market of the Russian Federation, there are pharmaceutical formulations with the active pharmaceutical substance salicylic acid. The use of selective SPE for analysis is a promising direction of research in drug quality control. Aim. Evaluation of the metrological characteristics of benzocaine quantitation by UV-spectrophotometry in certain pharmaceutical formulations using hypromellose sorbent for solid-phase extraction. Material and methods. The sorbent using a method developed by us was obtained. Salicylic acid (FS.2.1.0634, Russia State Pharmacopoeia XV ed.) to form active binding sites in sorbent structure was applied. The sorbent structure is polycyanoacrylate matrix with hypromellose fragments, the surface area is 255.50 m2/g, pore volume is 0.1433 cm3, pore diameter is 5.32 nm. The sorption capacity of hypromellose sorbent for benzocaine was 12.2 ± 0.8 μg/g. The SPE technique is proposed. SPE includes the stages: conditioning, sample addition and step-by-step elution with purified water and sodium hydroxide solution 0.1 mol/L. The spectrophotometer SF-56 was used to measure the absorbance at an analytical wavelength of 286 nm. To evaluate the selectivity (specificity) of sample preparation during chromatographic (SPE) separation of pharmaceutical formulations, absorption spectra of eluates in the wavelength range of 200-400 nm were scanned. The salicylic acid identification in the eluate was carried out based on absorption peaks at 228 and 298 nm.The salicylic acid calibration curve in the range of 1-20 μg/ml. To determination the metrological characteristics of salicylic acid quantitation method, 16 parallel determinations of samples of each pharmaceutical formulation were made. Statistical processing of the experimental results and determination of the metrological characteristics evaluation of analytical technique were carried out in accordance with general pharmacopoeial monograph (OFS.1.1.0013 "Statistical processing of results of physical, physicochemical, and chemical tests"). Results. When realizing the salicylic acid quantitation technique for measuring absorbance, it is advisable to use only the first portions of eluate (a solution of sodium hydroxide) in a volume of 5-10 ml were obtained. The relative error in determining the average content of salicylic acid in the analyzed preparations ranged from 1.18 to 1.44% for methods with solid-phase extraction (SPE) and 1.86-2.62% in its absence. It has been shown that there is a statistically significant difference in reproducibility for all preparations, as indicated by F-criteria values ranging from 7.81 to 13.5, exceeding their tabulated values. For the method without solid-phase extraction (SPE), there was an overestimation of the salicylic acid content in all cases, increasing the systematic error on average by 87.5%. Conclusion. The possibility of using a selective hypromellose sorbent for sample preparation for salicylic acid quantitation determination in pharmaceutical formulations has been showed. The use of sorbent for analysis provides to systematic error decrement of salicylic acid quantitation by an average of 87.5%.

APPLICATION OF SELECTIVE HYPROMELLOSE SORBENT FOR THE BENZOCAINE QUANTITATION IN PHARMACEUTICAL FORMULATIONS

Introduction. In quality control of pharmaceutical formulations, there are methodological approaches based on the preliminary separation of sample components and approaches without preliminary separation. The use of solid-phase extraction (SPE) allows to separate analytes during sample prepa-ration, with the separation selectivity determining the analysis selectivity as a whole. Currently, sorbents that provide selectivity in interaction with the analyte are of interest. Aim. Evaluation of the metrological characteristics of benzocaine quantitation by UV-spectrophotometry in certain pharmaceutical formulations using hypromellose sorbent for solid-phase extraction. Material and methods. The sorbent using a method developed by us was obtained. Benzocaine (FS.2.1.0634, Russia State Pharmacopoeia XV ed.) to form active binding sites in sorbent structure was applied. The sorbent structure is polycyanoacrylate matrix with hypromellose fragments, the sur-face area is 255.50 m2/g, pore volume is 0.1433 cm3, pore diameter is 5.32 nm. The sorption capacity of hypromellose sorbent for benzocaine was 12.2±0.8 μg/g. The SPE technique is proposed. SPE includes the stages: conditioning, sample addition and step-by-step elution with purified water and hydrochloric acid solution 0.1 mol/L. The spectrophotometer SF-56 was used to measure the absorbance at an analytical wavelength of 286 nm. To evaluate the selectivity (specificity) of sample preparation during chromatographic (SPE) separation of pharmaceutical formulations, absorption spectra of eluates in the wavelength range of 200400 nm were scanned. The benzocaine identification in the eluate was carried out based on absorption peaks at 220 and 286 nm. The benzocaine calibration curve in the range of 120 μg/ml. To determination the metrological characteristics of benzocaine quan-titation method, 11 parallel determinations of samples of each pharmaceutical formulation were made. Results. When realizing the benzocaine quantitation technique for measuring absorbance, it is advisable to use only the first portions of eluate (a solu-tion of hydrochloric acid) in a volume of 510 ml were obtained. The relative error of benzocaine average concentration in the pharmaceutical formula-tions ranged from 1.28 to 1.34% for technique that included the SPE stage, and from 1.86 to 2.02% for technique that did not include it. A comparison of the modifications of the spectrophotometric quantitation of benzocaine in pharmaceutical formulation using hypromellose sorbent and technique without the SPE did not reveal a statistically significant difference in reproducibility. For the modification technique without SPE, an increase of benzo-caine concentration and in determination relative error by an average of 48.0% were observed. Conclusion. The possibility of using a selective hypromellose sorbent for sample preparation for benzocaine quantitation determination in pharmaceu-tical formulations has been showed. The use of a sorbent for SPE at the sample preparation stage reduces the systematic error of benzocaine spectro-photometry quantitation for the analyzed pharmaceutical formulations by an average of 79.2%.

Rapid enantiomeric separation of indacaterol by electrokinetic chromatography

The first chiral methodology enabling the separation of indacaterol enantiomers was developed in this work by cyclodextrin-electrokinetic chromatography. Indacaterol (IND) is a chiral drug marketed as a pure enantiomer. Then, the separation and quantification of each enantiomer is of great importance for the quality control of pharmaceutical formulations. After selecting the most suitable chiral selector and background electrolyte, two Box-Behnken designs were achieved to optimize the electrophoretic conditions using two different approaches to shorten analysis times: i) decreasing the capillary length, or ii) performing a short-end injection. Indacaterol enantiomers were separated in less than 5 min with a resolution value of 3.6 under the optimal separation conditions: 0.7% (m/v) carboxymethyl-α-cyclodextrin in 50 mM sodium formate buffer (pH 4.0) and using a short-end injection. Then, the analytical characteristics of the method were evaluated and LODs of 0.05 mg/L for S-IND and 0.04 mg/L for R-IND were achieved. Also, the method allowed the detection of a 0.1% enantiomeric impurity (S-IND) in the R-IND-based pharmaceutical formulations. The developed method was applied to the analysis of two pharmaceutical formulations. Percentages of 97 ± 3% and 103 ± 6% of R-IND with respect to the labeled amounts were found.

New Green and High-throughput Microwell Spectrophotometric Method for Quality Control of Pharmaceutical Formulations of Selective Serotonin Reuptake Inhibitors via Microscale Formation of their N-Vinylamino-naphthoquinone Derivatives

Background: Selective serotonin reuptake inhibitors (SSRIs) are mostly prescribed for the treatment of depression. This study describes the microscale in-microwell formation of blue-colored N-vinylamino-naphthoquinone derivatives of SSRIs upon their reaction with 2,3-dichloro-1,4- naphthoquinone (DCNQ) and acetaldehyde. The reaction was subsequently utilized as a basis for the development of a new simple and sensitive microwell spectrophotometric method (MW-SPM) for the quality control of pharmaceutical formulations of four SSRIs. These SSRIs are fluoxetine (FLU), sertraline (SER), paroxetine (PAR), and reboxetine (REB). Methods: The MW-SPM procedure was performed in 96-microwell transparent plates, and the microplate reader was employed to measure the absorbances of the reaction products at their peak absorbance wavelength of 580 nm. The best conditions for the method were determined. Results: The relations showed good linearity (correlation coefficients were ≥0.9992) in the concentration range of 5 – 600 μg/mL. The limits of detection ranged from 5.20 to 15.58 μg/mL. The precision was deemed acceptable since all cases' relative standard deviation (RSD) values remained below 2.21%. Recovery experiments were conducted to confirm the accuracy of the method, yielding recovery values of at least 97.8%. The MW-SPM method was effectively utilized to analyze SSRIs in both their bulk and pharmaceutical dosage forms, exhibiting acceptable accuracy and precision. The recovery values ranged from 99.4% to 101.0% (with a margin of error of ± 0.5% to 1.6%). The results were comparable with those of the pre-validated reported methods. Four different metric tools evaluated the greenness of the proposed method, and the results proved that the method fulfills the requirements of green analytical approaches. Furthermore, the ability to handle numerous microvolume samples simultaneously in the described method provides it with a high-throughput characteristic. Conclusion: The proposed MW-SPM represents a valuable tool for an efficient analysis of SSRIs in pharmaceutical quality control units.

SUB-MINUTE CAPILLARY ZONE ELECTROPHORESIS METHOD FOR DETERMINATION OF HYDROCHLOROTHIAZIDE IN COMBINATION WITH OTHER ACTIVE INGREDIENTS IN NINE DIFFERENT PHARMACEUTICAL SAMPLES

Capillary electrophoresis (CE) methods have unique potential for applications in quality control of pharmaceutical formulations. Here, we show that a single and ultra-fast CE method can be used for the determination of hydrochlorothiazide (HCT) in combination with nine other active ingredients in a single run in different pharmaceutical samples: atenolol (ATE), metoprolol (MET), propranolol (PRO), benazepril (BEN), captopril (CAP), enalapril (ENA), lisinopril (LIS), ramipril (RAM), and valsartan (VAL). This goal was achieved using a single and simple background electrolyte (BGE) composed of 10 mmol L-1 of boric acid with pH adjusted to 9.0 with sodium hydroxide. All samples can be analyzed in less than 1 min with the attainment of good analytical performance, such as high-resolution separation (r > 1.3), low sample and reagents consumption (environmentally friendly method), low relative standard deviation (RSD) values for peak area (< 4.0%) and migration times (< 1.7%), and linear relationships with good correlation coefficients (> 0.995). Furthermore, recovery tests showed good results (100 ± 5%) for all evaluated compounds.

Validation of an HPLC-DAD Method for Quercetin Quantification in Nanoparticles.

The evaluation of the efficacy of incorporation of quercetin in nanoparticles is crucial, both for the development and quality control of pharmaceutical formulations. The validation of analytical methods for the precise quantification of quercetin is useful for the evaluation of various potential quercetin delivery systems and quercetin pharmacokinetics. This work aimed to validate a high-performance liquid chromatography with diode array detection (HPLC-DAD) method for quercetin detection and quantification in nanoparticles. Different mobile phase conditions and detection wavelengths (254 and 368 nm) were tested, and the major validation parameters were assessed (precision, accuracy, linearity, sensitivity, stability, and selectivity). The best peak resolution was obtained when quercetin was analyzed at 368 nm with a mobile phase of 1.5% acetic acid and a water/acetonitrile/methanol ratio of 55:40:5. Under these conditions, quercetin also eluted rapidly (retention time of 3.6 min). The method proved to be linear (R2 > 0.995), specific, and repeatable (variation coefficient between 2.4% and 6.7%) and presented intermediate precision (variation coefficient between 7.2% and 9.4%). The accuracy of the analysis ranged between 88.6% and 110.7%, and detection and quantification limits were 0.046 and 0.14 µg/mL, respectively. Quercetin solutions were more stable when stored at 4 °C than at room temperature or -20 °C. This validated method satisfied more parameters of bias assessment than most recent methods for quercetin determination and presented itself as more sensitive and efficient than general spectrophotometric methods. The method was successfully used for the analysis of quercetin incorporation in nanoparticles and will be evaluated in the future for its adequacy for the determination of quercetin in more complex matrices.

Spectrophotometric Study of Charge-Transfer Complexes of Ruxolitinib with Chloranilic Acid and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone: An Application to the Development of a Green and High-Throughput Microwell Method for Quantification of Ruxolitinib in Its Pharmaceutical Formulations

Ruxolitinib (RUX) is a potent drug that has been approved by the Food and Drug Administration for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. This study describes the formation of colored charge-transfer complexes (CTCs) of RUX, an electron donor, with chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the π-electron acceptors. The CTCs were characterized using UV-visible spectrophotometry. The formation of CTCs in methanol was confirmed via formation of new absorption bands with maximum absorption at 530 and 470 nm for CTCs with CLA and DDQ, respectively. The molar absorptivity and other physicochemical and electronic properties of CTCs were determined. The molar ratio was found to be 1:1 for both CTCs with CLA and CTCs with DDQ. The site of interaction on RUX molecules was assigned and the mechanisms of the reactions were postulated. The reactions were employed as basis for the development of a novel green and one-step microwell spectrophotometric method (MW-SPM) for high-throughput quantitation of RUX. Reactions of RUX with CLA and DDQ were carried out in 96-well transparent plates, and the absorbances of the colored CTCs were measured by an absorbance microplate reader. The MW-SPM was validated according to the ICH guidelines. The limits of quantitation were 7.5 and 12.6 µg/mL for the methods involving reactions with CLA and DDQ, respectively. The method was applied with great reliability to the quantitation of RUX content in Jakavi® tablets and Opzelura® cream. The greenness of the MW-SPM was assessed by three different metric tools, and the results proved that the method fulfills the requirements of green analytical approaches. In addition, the one-step reactions and simultaneous handling of a large number of samples with micro-volumes using the proposed method enables the high-throughput analysis. In conclusion, this study describes the first MW-SPM, a valuable analytical tool for the quality control of pharmaceutical formulations of RUX.

Simultaneous Estimation of Sacubitril and Valsartan Combination of Drug in Tablet Dosage Form Using Hydrotropy by UV Spectrophotometry

Sacubitril/valsartan, traded under the brand name Entresto between others, is a fixed-dose combination medication for use heart failure. Sacubitril is a neprilysin inhibitor (A prodrug) and is used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure. It is anti - hypertensive drug. Valsartan is an Angiotensin Receptor Blocker (ARB) that may be used to treat a variety of cardiac conditions including hypertension, diabetic nephropathy and heart failure. Two UV-spectrophotometric methods have been developed and validated for simultaneous estimation of Sacubitril and Valsartan in a tablet dosage form. The first method employed solving of simultaneous equations based on the measurement of absorbance at two wavelengths, 226.0 nm and 254.0 nm, 𝜆max for Sacubitril and Valsartan, respectively. The second method was absorbance ratio method, which involves formation of Q-absorbance equation at 240 nm (isoabsorptive point) and also at 254 nm (𝜆max of Valsartan). The methods were found to be linear between the range of 4-12 𝜇g/mL for Sacubitril and 2-10 𝜇g/mL for Valsartan using Methanol as solvent. The mean percentage recovery was found to be 96.68%and 101.89% for the simultaneous equation method and 100.2% and 104.53% for the absorbance ratio method, for sacubitril and valsartan respectively. It could be concluded from the results obtained in the present investigation that the two methods for simultaneous estimation of sacubitril and valsartan in tablet dosage form are simple, rapid, accurate, precise and economical and can be used, successfully, in the quality control of pharmaceutical formulations and other routine laboratory analysis. The reviewed highlights various analytical techniques such as high-performance liquid chromatography (HPLC), ultra- performance liquid chromatography (UPLC), UV Spectroscopy, high per-formance thin layer chromatography (HPTLC), liquid chromatography coupled to tandem mass spectrometry (LC- MS), RP-HPLC and other chromatographic method used. The combination of these drugs with different method was examine and the commonly use of the drugs in hypertensive.

An intelligent approach based on hybrid of principal component analysis-fuzzy inference system-adaptive neuro-fuzzy inference system for the simultaneous spectrophotometric determination of sofosbuvir and velpatasvir as antiviral drugs in pharmaceutical formulation and urine sample

In this study, a simple, fast, accurate, and inexpensive chemometrics-assisted spectrophotometric method was developed for the simultaneous determination of sofosbuvir (SOF) and velpatasvir (VEL) as antiviral drugs. Fuzzy inference system (FIS) and adaptive neuro-fuzzy inference system (ANFIS) along with principal component analysis (PCA) were used for the analysis of SOF and VEL in binary mixtures, pharmaceutical formulation, and urine sample. Root mean square error (RMSE) of FIS model was 0.1518 and 0.075 for SOF and VEL, respectively. Also, the average testing error related to the ANFIS method was achieved 2.23 ​× ​10−5 and 5.58 ​× ​10−6 for SOF and VEL, respectively. The range of mean recovery percentage was between 99.76 and 100.41 for both methods. Relative standard deviation (RSD) of the real sample was lower than 0.06% for FIS and ANFIS for both components. Analysis of variance (ANOVA) was applied to the results of the real sample that there was no significant difference between the suggested approaches. PCA-FIS and PCA-ANFIS as efficient and accurate methods can be useful for the simultaneous estimation of binary and ternary mixtures in quality control of pharmaceutical formulations.

Melanochrome-based colorimetric assay for quantitative detection of levodopa in co-presence of carbidopa and its application to relevant anti-Parkinson drugs.

In this paper is reported the selective detection and quantification of levodopa in co-presence of carbidopa. The method took advantage of the spontaneous oxidation and color development of levodopa at basic pH here driven by alkaline earth cations and co-solvent in solution. We have shown for the first time the generation and stabilization of the purple melanochrome from levodopa, by using magnesium acetate and dimethyl sulfoxide, which was here exploited for the development of a quantitative colorimetric assay for the active principle ingredient in commercial drugs for the treatment of Parkinson's disease. The calibration curves of levodopa in the two tablet formulations, containing carbidopa as decarboxylase inhibitor, showed a common linear trend between 10 mg L-1 and 40 mg L-1 with levodopa alone or in combination with carbidopa in standard solutions, with very good reproducibility (CVav%, 3.3% for both brand and generic drug) and very good sensitivity, with limit of quantification about 0.6 mg L-1 in any case. The colorimetric method here developed is very simple and effective, appearing as a rapid and low-cost alternative to other methodologies, involving large and expensive instrumentations, for drug estimation and quality control of pharmaceutical formulations.

Determination of Tedizolid Phosphate Using Graphene Nanocomposite Based Solid Contact Ion Selective Electrode; Green Profile Assessment by Eco‐scale and GAPI Approach

AbstractAntibiotics determination plays a major role in minimizing antimicrobial resistance starting from quality control of pharmaceutical formulations to therapeutic drug monitoring. Green modified glassy carbon electrode has been developed for determination of tedizolid phosphate; new antibiotic prodrug; in presence of its active metabolite. The graphene transducer interlayer, dispersed with PVC, improved the electrode stability and standard potential reproducibility. Graphene hydrophobicity prevented the water layer formation between the sensing layers that decreased the potential drift down to 267 μV h−1. Electrochemical impedance showed a low resistance value for graphene containing sensor due to its high electron transfer ability.

A Review of Analytical Methods for Codeine Determination.

Codeine is derived from morphine, an opioid analgesic, and has weaker analgesic and sedative effects than the parent molecule. This weak opioid is commonly used in combination with other drugs for over-the-counter cough relief medication. Due to the psychoactive properties of opioid drugs, the easily obtained codeine often becomes subject to misuse. Codeine misuse has emerged as a concerning public health issue due to its associated adverse effects such as headache, nausea, vomiting, and hemorrhage. Thus, it is very important to develop reliable analytical techniques to detect codeine for both quality control of pharmaceutical formulations and identifying drug misuse in the community. This review aims to provide critical outlooks on analytical methods applicable to the determination of codeine.

Disposable Pencil Graphite Electrode for Ciprofloxacin Determination in Pharmaceutical Formulations by Square Wave Voltammetry

AbstractIn this work, a new electrochemical sensor based on pencil graphite with interesting features, such as low cost (US$ 0.01 per electrode), ease manufacture, and portability was developed. The sensor showed an adequate manufacturing reproducibility with RSD <5.3 %. Under this electrochemical platform, ciprofloxacin underwent an irreversible oxidation process at 1.03 V, characterized by the diffusion of electroactive species. A simple method by square wave voltammetry (SWV) has been optimized for the determination of ciprofloxacin in pharmaceutical formulations using a pencil graphite electrode (PGE). The method showed satisfactory analytical performance, with a wide linear range (12 to 55 μmol L−1), low detection limit (5.6 μmol L−1), adequate precision (RSD <3.2 %), and accuracy with an average recovery of (102±15)%. Samples of pharmaceutical formulations were evaluated, obtaining levels of ciprofloxacin close to those established by the manufacturers. In addition, the samples were analyzed by liquid chromatography and there was no significant difference between the methods at the 95 % confidence level. In this sense, the method developed proved to be reliable and promising for the quality control of pharmaceutical formulations.

Development of Electrochemical Biosensor Based on Nanostructured Carbon Materials for Paracetamol Determination

AbstractThis work describes the development of a biosensor for paracetamol (PAR) determination based on a glassy carbon electrode (GCE) modified with multiwalled carbon nanotubes (MWCNT) and laccase enzyme (LAC), which was immobilized by means of covalent crosslinking using glutaraldehyde. Voltammetric investigations were carried out by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV). The biosensor was characterized by Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectroscopy (FT‐IR). The results showed that the use of MWCNT/LAC composite increased the sensor sensitivity, compared to bare glassy carbon electrode. Factors affecting the voltammetric signals such as pH, ionic strength, scan rate and interferents were assessed. Linear range, limit of detection (LOD) and limit of quantitation (LOQ) obtained were 10–320 μmol L−1, 7 μmol L−1 and 10 μmol L− 1, respectively. The developed biosensor was successfully applied to PAR determination in urine and pharmaceutical formulations samples, with recovery varying from 99.96 to 106.20 % in urine samples and a relative standard deviation less than 1.04 % for PAR determination in pharmaceutical formulations. Therefore, the MWCNT‐LAC/GCE exhibits excellent sensitivity and can be used to PAR determination as a viable alternative in clinical analyzes and quality control of pharmaceutical formulations, through a simple, fast and inexpensive methodology.

Poly(propylene glycol) stabilized gold nanoparticles: An efficient colorimetric assay for ceftriaxone

Polymer capped metal nanoparticles have been used for numerous biomedical and analytical applications. In present study, highly stable gold nanoparticles (AuNPs) capped with polypropylene glycol (PPG) were synthesized using chemical reduction method. The characterization of PPG-AuNPs was accomplished by atomic force microscopy (AFM), zetasizer, fourier transform infrared spectroscopy (FT-IR) and UV–vis spectroscopy. Furthermore, PPG-AuNPs were utilized as colorimetric probe for third generation cephalosporin antibiotic, ceftriaxone (CEF). PPG-AuNPs permitted efficient, selective, quantitative and rapid recognition in concentration range of 0.1–100μM in presence of numerous other drugs and salts. PPG-AuNPs have great potential for quantitative recognition of ceftriaxone in biological and environmental samples. Moreover, the developed sensor has capacity to be applied as quality control of pharmaceutical formulations containing ceftriaxone. The PPG-AuNPs based sensor permits quantitative and fast recognition of ceftriaxone away from a sophisticated laboratory setup.

DETERMINATION OF DOXORUBICIN HYDROCHLORIDE IN PHARMACEUTICA DOSAGE FORMS BY A SIMPLE STABILITY-INDICATING MICELLAR ELECTROKINETIC CAPILLARY CHROMATOGRAPHY METHOD

A stability-indicating micellar electrokinetic capillary chromatography (MEKC) method was developed and validated for the analysis of doxorubicin hydrochloride in injectable pharmaceutical dosage forms, using methotrexate as internal standard. A fused-silica capillary (50 µm i.d.; effective length, 40 cm) and a running electrolyte solution consisting of 10 mM borate buffer and 20 mM anionic surfactant SDS, at pH 9.3, were set as the best experimental conditions. Moreover, the capillary temperature was maintained at 26 ºC, while the applied voltage was +26 kV. Hydrodynamic sample injection (6 s at 50 mbar) was used, and the detection was set at 260 nm using a photodiode array detector. The method was validated for the requirements specificity, linearity, precision, accuracy, and robustness, following the International Conference on Harmonisation (ICH) guidelines. The method linearity was proven in the range of 25-125 µg/mL (r = 0.9995). Forced degradation studies were successfully conducted, evidencing the specificity and stability-indicating capability of the method. In addition, no interference of the excipients from the formulation was detected. The values of accuracy and precision were within the acceptable limits, and robustness studies were performed by a two-level full factorial design. The proposed method fulfilled all validation parameters and was shown to be suitable for quantitative analyses of doxorubicin, contributing, thus, to the establishment of new alternatives with advantages for the quality control of pharmaceutical formulations.

High-throughput amperometric determination of tetracycline residues in milk and quality control of pharmaceutical formulations: flow-injection versus batch-injection analysis

This paper demonstrates a potential use of the reduced graphene-oxide modified electrode associated with FIA and BIA systems for rapid, simple and sensitive determination of tetracycline in milk and pharmaceutical formulations samples.

Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Haloperidol and Trihexyphenidyl in API and Combined Tablet Dosage Form

A rapid and precise reverse phase high performance liquid chromatographic method has been developed for the validated of Trihexyphenidyl and Haloperidol, in its pure form as well as in tablet dosage form. Chromatography was carried out on a Altima C18 (4.6 x 150mm, 5μm) column using a mixture of Methanol: TEA Buffer pH 4.5: Acetonitrile (50:25:25) as the mobile phase at a flow rate of 1.0ml/min, the detection was carried out at 225 nm. The retention time of the Trihexyphenidyl and Haloperidol was 2.102, 3.537±0.02min respectively. The method produce linear responses in the concentration range of 15-75ppm of Trihexyphenidyland 37.5-187.5ppm of Haloperidol. The method precision for the determination of assay was below 2.0%RSD. The method is useful in the quality control of pharmaceutical formulations.

DEVELOPMENT AND VALIDATION OF UV-SPECTROPHOTOMETRIC METHOD FOR ESTIMATION OF HYDROQUINONE IN BULK, MARKETED CREAM AND PREAPARED NLC FORMULATION

Objective: The aim of the present work was to develop a simple, rapid, accurate and economical UV-visible spectrophotometric method for the determination of hydroquinone (HQ) in its pure form, marketed formulation as well as in the prepared nanostructured lipid carrier (NLC) systems and to validate the developed method.Methods: HQ was estimated at UV maxima of 289.6 nm in pH 5.5 phosphate buffer using UV-Visible double beam spectrophotometer. Following the guidelines of the International Conference on Harmonization (ICH), the method was validated for various analytical parameters like linearity, precision, and accuracy robustness, ruggedness, limit of detection, quantification limit, and formulation analysis.Results: The obtained results of the analysis were validated statistically. Recovery studies were performed to confirm the accuracy of the proposed method. In the developed method, linearity over the concentration range of 5-40 μg/ml of HQ was observed with the correlation coefficient of 0.998 and found in good agreement with Beer Lambert’s law. The precision (intra-day and inter-day) of the method was found within official RCD limits (RSD<2%).Conclusion: The sensitivity of the method was assessed by determining the limit of detection and limit of quantification. It could be concluded from the results obtained that the purposed method for estimation of HQ in pure form, in the marketed ointment and in the prepared NLC-formulation was simple, rapid, accurate, precise and economical. It can be used successfully in the quality control of pharmaceutical formulations and for the routine laboratory analysis.