High-pressure Liquid Chromatographic Method Research Articles

NEW RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF ANTIFUNGAL DRUG ITRACONAZOLE IN ITRACONAZOLE LOADED INVASOMES GEL

A new simple, accurate, rapid, selective and robust high pressure liquid chromatography (HPLC) method was developed and validated for estimation of itraconazole (ITZ) in bulk and prepared in house invasomes gel formulation. Acetonitrile and Methanol was used as a mobile phase for chromatographic separation in the ratio of 20mM KH2PO4: Acetonitrile (pH adjusted to 4.0 with OPA) at flow rate of 1.0 ml/min and estimation on Thermo C18 (250 × 4.6 mm) in the ratio of 50:50 v/v at flow rate of 1.0 ml/min. The detection was carried out with UV detector set at 262nm. The retention time for itraconazole was found to be 2.258±0.095 minutes. The linearity range for itraconazole was found to be 5-25 μg/ml with coefficient of linear regression 0.998. The method was validated in accordance with the requirements of International Conference on Harmonization (ICHQ2 A 8 B) guidelines for specificity, linearity, accuracy, precision, LOD 8 LOQ.

Chiral organic stereochemistry: Chiral HPLC, chiral auxiliaries, CD spectroscopy, X-ray crystallography, and light-powered chiral molecular motors.

In the studies of chiral organic stereochemistry, it is important to use enantiopure compounds. For this purpose, the chiral HPLC (High-Pressure Liquid Chromatography) columns containing chiral stationary phases were invented by Y. Okamoto and coworkers for enantio-separating various racemic compounds. In addition, the use of chiral auxiliaries is also useful for preparing enantiopure compounds and also for determining their absolute configurations, where covalent-bonded diastereomers are separated by HPLC on silica gel. In this review article, these HPLC methods will be discussed together with the applications to some interesting organic compounds including light-powered chiral molecular motors.

Characteristics of Collagen Preparations from Leather Wastes by the High Pressure Liquid Chromatography Method

The raw trimming waste from the leather industry is considered potential hazardous waste as a consequence of the chrome tanned leather process. On the other hand, leather waste contains a large amount of precious protein – collagen, which has many uses. Nowadays, collagen preparations obtained from leather waste are available on the market. This paper presents a procedure for the determination of amino acids in five collagen preparations of animal origin. Recent improvements in HPLC-based methods for analysing amino acids have made it feasible to analyse different sample types accurately. In this study the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization procedure was applied. The amino acid analysis indicated the presence of 18 amino acids (Asp, Ser, Glu, His, Gly, Arg, Thr, Ala, Pro, Cys, Tyr, Val, Lys, Met, Ile, Leu, Phe and Hyp) in the collagen samples. Glycine, alanine, proline and hydroxyproline were the most abundant amino acid, whereas the lowest contents corresponded to serine, tyrosine, valine and izoleucine. The analysis proposed can be used with confidence in collagen quality control to guarantee appropriate amino acid content.

New Validated Method for the Estimation of Pioglitazone and Rosiglitazone Using RP-HPLC

New, simple and economical high pressure liquid chromatography method has been developed for the simultaneous quantification of Pioglitazone and Rosiglitazone.By using Waters HPLC e-2695 quaternary pump with a PDA detector of 2998 instrument the chromatographic separation of Pioglitazone and Rosiglitazone was achieved on the column of Inertsil ODS (150x4.6mm, 3.5 µ) using an isocratic elution with a buffer containing 0.1percentformic acid and acetonitrile at a rate of 30:70 as a mobile phase with a flow rate of 1 ml/min at ambient temperature. A detector wavelength of 261 nm utilizing the PDA detector were given in the instrumental settings. The linearity was studied between the concentration range of 3-45 µg/ml of Pioglitazone and 1-15 µg/ml of Rosiglitazone were injected.The plotted calibration curves were linear with a regression coefficient of R2> 0.999, indicates that the linearity was with in the limit. As a part of method validation the parameters like specificity, linearity, accuracy, ruggedness, robustness were determined and the results were found to be within the allowable limit. The method developed was found to be applicable to routine analysis and to be used for the measurement of both active pharmaceutical ingredients (i.e, Pioglitazone and Rosiglitazone).Validation of the proposed method was carried out according to an International Conference on Harmonization (ICH) guidelines. Since, there is no HPLC method reported in the literature for the estimation of Pioglitazone and Rosiglitazone, there is a need to develop quantitative methods under different conditions to achieve improvement in specificity, selecivity etc.

High Pressure Liquid Chromatographic Method for the Determination of Mobocertinib in Pharmaceutical Dosage Form and Study of Its Degradation

Aims: New validated method for the estimation of Mobocertinib using HPLC and study of its degradation.
 Place and Duration of Study: Department of Chemistry, RVR & JC College of Engineering, Chowdavaram, Guntur, Andhra Pradesh, between February 2021 and August 2021.
 Methodology: Using an X-bridge phenyl column (150 mm x 4.6 mm, 3.5 µ), acetonitrile, and 0.1 percent ortho phosphoric acid (OPA) (60:40 v/v) as a mobile phase, the proposed method successfully achieved effective chromatographic separation with a flow rate of 1 mL/min and a wave length of 224 nm. Mobocertinib had a retention time of 2.271 minutes. The isocratic chromatography was performed at room temperature and took approximately five minutes to complete.
 Results: Analysis was achieved within 5 min over an honest linearity within the concentration range from 6-90 µg/ml of Mobocertinib. Using a mathematical process, the suitability parameters of the system were investigated, and the results were found to be in acceptable limits. In a linear analysis, stages with regression coefficients of 0.999 were used. LOD and LOQ values were 0.075μg/ml and 0.248 g/ml for Mobocertinib. The drug was recovered at a rate of 98-102 percent, which means that the recovery is within reasonable limits.
 Conclusion: The validation results were satisfactory, and the approach was found to be suitable for bulk and formulation analysis. The recommended procedure was found to be warranted according to ICH guidelines.

Method development and validation for simultaneous estimation of amlodipine besylate and enalapril maleate in solid dosage form

A rapid, sensitive, specific, accurate and precise high pressure liquid chromatographic method (HPLC) method involving UV detection has been developed for the determination and quantification of Amlodipine Besylate and Enalapril maleate in bulk and combined dosage form. The determination was carried out on a Phenomenex C18 column (Dimention : 250 x 4.6 mm, 5 μm). The sample was analysed using filtered and degassed mixture of methanol : 0.1N HCl (1:1) as mobile phase at a flow rate of 1ml/min and effluent was monitored at 218nm. The retention time for Amlodipine besylate was 7.6 min and for Enalapril maleate 3.2 min. Amlodipine besylate and Enalapril maleate showed a linear response in the concentration range of 10-50μg/ml. The correlation co-efficient ('r' value) for Amlodipine besylate and Enalapril maleate was 0.9992 and 0.9994, respectively. The method was validated in terms of linearity, precision, accuracy, specificity, robustness and solution stability. The proposed method can be used for routine analysis of Amlodipine Besylate and Enalapril maleate in bulk and combined dosage form

DoE-Based Analytical Quality Risk Management for Enhanced AQbD Approach to Economical and Eco-Friendly RP-HPLC Method for Synchronous Estimation of Multiple FDC Products of Antihypertensive Drugs.

According to the literature review, numerous chromatographic methods have been published for estimation of fixed-dose combination products of telmisartan but no reverse-phase high-pressure liquid chromatographic (RP-HPLC) method has been published yet for synchronous estimation of fixed-dose combination (FDC) products of telmisartan to save time, cost and solvent for analysis. Hence, an economical and eco-friendly RP-HPLC method has been developed for synchronous estimation of multiple FDC products of antihypertensive drugs using the quality risk management (QRM) and DoE-based enhanced analytical quality by design approach. The analytical-QRM was started with the identification of potential method risk parameters followed by their risk assessment by risk priority number ranking and filtering. The identified critical method parameters were optimized using the DoE-based central composite design. The method operable design range was navigated and the control strategy was framed for control and mitigation of risk throughout the life-cycle of the developed method. The method was developed using Shimpack Octadecyl silane (ODS) C18 column and acetonitrile-1.0%v/v triethylamine in water (pH6.0; 45 + 55, %v/v). The developed method was validated as per the International Council for Harmonization Q2 (R1) guideline. The developed method was applied for the analysis of seven different antihypertensive dosage forms. The developed RP-HPLC method can be used as an eco-friendly, robust and economical alternative analytical tool to several published methods for estimation of FDC products of antihypertensive drugs in the pharmaceutical industry.

A Validated RP-HPLC Method for the Determination of Butamirate Citrate and Benzoic Acid in Syrup, Based on an Experimental Design Assessment of Robustness

A reversed-phase high-pressure liquid chromatography (RP-HPLC) method was developed and subsequently validated for the simultaneous determination of butamirate citrate (BC) and benzoic acid (BA) in cough syrup. The separation was performed employing a cyanopropyl column with a mobile phase consisting of 50%/50% v/v MeOH/NaH2PO4 * H2O 50 mM aqueous solution pH = 3.0. The quantitation was achieved with a diode array detector (DAD) at 210 nm. The method demonstrated a congenitally satisfactory separation, yet the acquired peaks were asymmetrical. This effect was eliminated by using 1% triethylamine in the buffer solution as a silanol blocker. In addition, the method was found to unequivocally assess the target analytes in the sample matrix and fulfilled the required specifications in relevance to specificity, linearity, accuracy, precision and stability of both the standard solutions and of the sample solutions. Lastly, an experimental design was designed in order to assess the robustness of the proposed assay. To this purpose, a graphical and a statistical approach were utilized and compared to identify the factors that should be strictly controlled during each execution of the method.

Stability Demonstrating Validated High Pressure Liquid Chromatographic Method for the Determination of Trilaciclib in Bulk and Pharmaceutical Formulation

Aims: New validated method for the estimation of Trilaciclib using HPLC and study of its degradation
 Place and Duration of Study: Department of Chemistry, RVR & JC College of Engineering, Chowdavaram, Guntur, Andhra Pradesh, between February 2021 and August 2021.
 Methodology: Using an inertsil ODS column (150 mm x 4.6 mm, 3.5 µ), acetonitrile, and 0.1 percent ortho phosphoric acid (OPA) (50:50 v/v) as a mobile phase, the proposed method successfully achieved effective chromatographic separation with a flow rate of 1 mL/min and a wave length of 220 nm. Trilaciclib had a retention time of 4.358 minutes. The isocratic chromatography was performed at room temperature and took approximately six minutes to complete.
 Results: Analysis was achieved within 6 min over an honest linearity within the concentration range from 3-45 µg/ml of Trilaciclib. Using a mathematical process, the suitability parameters of the system were investigated, and the results were found to be in acceptable limits. In a linear analysis, stages with regression coefficients of 0.999 were used. LOD and LOQ values were 0.038 μg/ml and 0.124 g/ml for trilaciclib. The drug was recovered at a rate of 98-102 percent, which means that the recovery is within reasonable limits.
 Conclusion: The validation results were satisfactory, and the approach was found to be suitable for bulk and formulation analysis. The recommended procedure was found to be warranted according to ICH guidelines.

HPLC Fingerprints for the Characterization of Walnuts and the Detection of Fraudulent Incidents.

A high-pressure liquid chromatographic method coupled to diode array detector (HPLC-DAD) was developed for the determination of phenolic compounds that could be used as markers in authentication studies of walnuts belonging to the Chandler variety, originating from Bulgaria, Greece, and France. An ultrasound-assisted extraction (UAE) protocol applied in the extraction of phenolic compounds was optimized. The method was validated and the relative standard deviations (RSD%) of the within-day, and between-day assays was lower than 6.3 and 11.1, respectively, showing adequate precision, and good accuracy ranging from 86.4 (sinapic acid) to 98.4% (caffeic acid) for within-day assay, and from 90.1 (gallocatechin gallate) to 100.6% (gallic acid) for between-day assay. Eighteen phenolic compounds were determined belonging to the classes of phenolic acids and flavonoids. The quantification results were further processed with chemometrics, and a robust partial least square–discriminant analysis (PLS-DA) model was developed for the classification of the samples according to their geographical origin, proposing markers that could be used for the control of walnuts authenticity and the detection of fraudulent incidents.

NEW VALIDATED METHOD FOR THE ESTIMATION OF ALLANTOIN AND PERMETHRIN USIGN RP-HPLC IN BULK AND PHARMACEUTICAL DOSAGE FORM

Objective: Special, effective high pressure liquid chromatography method has been developed for the simultaneous quantification of Allantoin and Permethrin. Methods: By using Waters HPLC e-2695 quaternary pump with a PDA detector of 2998 instrument the chromatographic separation of Allantoin and Permethrin was achieved on the column of Symmetry C18 (150x4.6 mm, 3.5 µm) using an isocratic elution with a buffer containing 0.1percent ortho phosphoric acid and acetonitrile at a rate of 40:60 as a mobile phase with a flow rate of 1 ml/min at ambient temperature. A detector wavelength of 226 nm utilizing the PDA detector were given in the instrumental settings. The linearity was studied between the concentration range of 1-15 µg/ml of Allantoin and 25-375 µg/ml of Permethrin were injected with a run time of 6 min. As a part of method validation the parameters like specificity, linearity, accuracy, ruggedness, robustness were determined and the results were found to be within the allowable limit. Validation of the proposed method was carried out according to an International Conference on Harmonization (ICH) guidelines. Results: LOD and LOQ for the two active ingredients were established with respect to test concentration. The plotted calibration curves were linear with a regression coefficient of R2>0.999, indicates that the linearity was with in the limit. As a part of method validation the parameters like specificity, linearity, accuracy, ruggedness, robustness were determined and the results were found to be within the allowable limit. Conclusion: The method developed was found to be applicable to routine analysis and to be used for the measurement of both active pharmaceutical ingredients (i. e, Allantoin and Permethrin). Since, there is no HPLC method reported in the literature for the estimation of Allantoin and Permethrin, there is a need to develop quantitative methods under different conditions to achieve improvement in specificity, selecivity etc.

Analytical Method Development and Validation for Simultaneous Determination of Simvastatin and Mupirocin Using Reverse-Phase High-pressure Liquid Chromatographic Method

This study was aimed to develop and validate the use of reverse-phase high pressure liquid chromatographic method for the estimation of simvastatin (SIM) and mupirocin (MUP) simultaneously. The chromatographic method developed is optimized for flow rate with the column, solvent, and buffer used and mobile phase ratio, molarity, and pH. The validation of the optimized method and the forced degradation studies of both drugs (under acidic, alkaline, oxidation, heat, light, and neutral conditions) were conducted following the The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. Kromasil C18 column (250 mm × 4.6 mm, 5 µm) with ultraviolet detection at 224 nm and acetonitrile/phosphate buffer (30 mM, 70:30 v/v, pH 3.5; adjustment done using orthophosphoric acid) as mobile phase at a flow rate of 1.1 mL/min were observed to provide a good resolution for MUP and SIM at retention times of 2.32±0.008 and 13.55±0.254 min, respectively, with high accuracy (percent recovery was 99.69±0.82 for MUP and 101.10±0.02 for SIM) and linearity in the range of 5-30 µg/mL (r2: 0.9969 for MUP and r2: 0.9959 for SIM). The diagnostic limit and the lower limit of determination were 0.771±0.234 and 2.338±0.246 μg/mL for MUP and 0.595±0.282 and 1.803±0.334 µg/mL for SIM, respectively. The validated method was used to understand the degradation behavior of both drugs after the forced degradation studies. The analytical method developed is determined to be specific, sensitive, precise, and accurate for the estimation of MUP and SIM simultaneously in the combined dosage form.

합성제올라이트의 폼알데하이드 흡착능 평가

In this study, the adsorption capacity of formaldehyde was analyzed by using Activated Carbon and five types of synthetic zeolite. The experiments were conducted according to 2,4-dinitrophenylhydrazine (DNPH) derivatization and high pressure liquid chromatography (HPLC) methods for analysis of formaldehyde. The adsorption capacity of formaldehyde was discussed by outflow/inflow of concentration, amount of adsorption per gram of adsorbent, averaged removal rate and economic evaluation. Total amount of adsorption per gram of adsorbent decreased steadily for increasing the fill amount of adsorbent. The most amount of adsorption was represented for Beta Zeolite Fe, but the economic evaluation was relatively high for Zeolite A. Activated Carbon showed relatively superior persistence of adsorption in the adsorption experiment for 200 minutes. The stability of adsorption was evaluated to relatively superior for Zeolite X in the repeated experimental results of the 20 minutes adsorption for formaldehyde. This study suggested that the selective use of various synthetic zeolite may be useful for formaldehyde removal considering adsorption capacity and economic feasibility.

A Purification Method of 18F-FP-(+)-DTBZ via Solid-Phase Extraction With Combined Cartridges

Background: To optimize [18F] 9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) purification via solid-phase extraction (SPE) with combined cartridges to facilitate its widespread clinical application.Methods: A modified SPE purification method, employing Sep-Pak PS-2 and Sep-Pak C18 cartridges, was used for the preparation of 18F-FP-(+)-DTBZ. This method was compared to the purification method of high-pressure liquid chromatography (HPLC) and SPE with one cartridge, following quality control test and positron emission tomography (PET) imaging in healthy volunteers and patients with parkinsn's disease (PD).Results: A SPE purification method integrating Sep-Pak PS-2 and Sep-Pak C18 cartridges was implemented successfully. The retention time of 18F-FP-(+)-DTBZ purified by HPLC, SPE with Sep-Pak PS-2, SPE with Sep-Pak C18, and SPE with combined use of Sep-Pak PS-2 and Sep-Pak C18 cartridges was 8.7, 8.8, 8.7, and 8.9 min, respectively. Fewest impurity peak was detected in 18F-FP-(+)-DTBZ purified by the SPE with combined use of Sep-Pak PS-2 and Sep-Pak C18 cartridges. This modified SPE purification method provided a satisfactory radiochemical yield of 29 ± 1.8% with radiochemical purity >99% and shortened synthesis time to 27 min. The brain uptake of 18F-FP-(+)-DTBZ purified by the modified SPE was comparable to that purified by HPLC in both healthy volunteers and PD patients.Conclusions: A SPE method integrating Sep-Pak PS-2 and Sep-Pak C18 cartridges for purification of 18F-FP-(+)-DTBZ may be highly suited to automatic synthesis for routine clinical applications, as it provides excellent radiochemical purity, high yield as well as operational simplicity.

Stability study of concentrate-solvent mixture & infusion solutions of Jevtana® cabazitaxel for extended multi-dosing.

In this study, the prolonged physical and chemical stability of the anticancer agent cabazitaxel, commercially available as Jevtana®, was examined. Both concentrate-solvent mixture and infusion solution were examined with the aim to extend the use of multidose left-over cabazitaxel and infusion solutions and with that reduce financial and environmental waste. A validated stability-indicating high-pressure liquid chromatography (HPLC) method with ultraviolet (UV) and photodiode array (PDA) detection was used to examine the purity and any degradation of cabazitaxel. The concentrate-solvent mixture and infusion solution samples that were tested had been stored out of the range of the criteria stated in the summary of product characteristics (SmPC). The concentrate-solvent mixtures were stored at 3-5°C, 18-21°C, and 40 °C, whereas the infusion solution was stored at 3-5°C. All samples were tested at t = 0, t = 1 week and t = 2 weeks. All samples showed that purity and concentration had remained within the criteria of <5% as stated in the European Pharmacopoeia. However, the concentrate-solvent mixtures stored at 18-21°C and 40 °C showed a degradation product forming in all the samples lowering the purity of the samples from 100% to 99.91% and 98.20% respectively, whereas all samples stored at 3-5°C remained at 100%. Concentrate-solvent mixture and infusion solution of cabazitaxel, Jevtana®, can be used up to 2 weeks after preparation if stored at 3-5°C and prepared under aseptic conditions.

Analytical quality by design approach for the control of potentially counterfeit chloroquine with some NSAIDS using HPLC with fluorescence detection in pharmaceutical preparation and breast milk

AbstractChloroquine phosphate (CQ) the antimalarial drug and suggested to treat the pandemic disease coronavirus (COVID-19) is often adulterated with some of the non-steroidal anti-inflammatory drugs (NSAIDs) such as paracetamol, aspirin (ASP), or both. The purpose of this study is to detect such counterfeited drugs, using a reversed phase high pressure liquid chromatography (RP-HPLC) method with fluorescence detection. Analysis was divided into three phases. In the first phase, a Plackett-Burman design (PBD) was used to screen five independent factors, namely, buffer pH, buffer concentration (mM), acetonitrile content (%), flow rate (mL/min) and triethylamine (TEA) content in the buffer preparation (%). The selected dependent variables were (resolution, symmetry of peaks and run time). The objective of the second phase was to optimize the method performance using Box-Behnken design (BBD) and desirability function for multiple response optimization to obtain the best chromatographic performance with the shortest run time. Optimal chromatographic separation was achieved on a YMC-pack pro C18 ODS-A column (15 cm × 4.6 mm, 5 µm) at room temperature The optimum mobile phase consisted of acetonitrile and 5 mM sodium dihydrogen phosphate buffer containing 0.5% triethyamine (30:70, v/v) with the pH adjusted to 3.5 using an orthophosphoric acid solution. The flow rate was maintained at 1 mL/min, and the detection was performed with a fluorescence detector fixed at 380 nm (λemission) after excitation at 335 nm (λexcitation). The third phase was method validation according to ICH guidelines, providing to be specific, precise, accurate, and robust. The method is linear over a range of 0.4–8 µg/mL for chloroquine and ASP, while for paracetamol it is linear over 16–48 µg/mL. The developed RP-HPLC method was used for quantitation of the three drugs in chloroquine dosage form samples. The method shows a great tendency in the classification between the genuine chloroquine and the adulterated ones in pharmaceutical preparations and breast milk.

Development of an ivermectin-containing syrup as an extemporaneous preparation for treatment of scabies in children

HintergrundZur Therapie der Skabies kann orales Ivermectin eingesetzt werden. Die Evidenz für einen sicheren und wirksamen Einsatz bei Kleinkindern im Einzelheilversuch ist erarbeitet worden und publiziert. Um eine körpergewichtsadaptierte Dosierung auch für Kinder zu gewährleisten, wurde ein Ivermectin-haltiger Saft als Magistralrezeptur entwickelt.Material und MethodenDa Ivermectin nicht als Reinsubstanz für die Rezeptur zur Verfügung steht, wurden wirkstoffhaltige Tabletten als Ausgangsmaterial für die Entwicklung benutzt. Die Formulierung wurde entsprechend pharmazeutischer, regulatorischer und gebrauchsorientierter Kriterien konzipiert. Zum Nachweis der chemischen Stabilität wurde eine HPLC(Hochleistungsflüssigkeitschromatographie)-Methode erarbeitet und validiert. Um die praktische Umsetzung zu erleichtern, wurden zudem Angaben zu geeigneten Packmitteln und zu Applikationshilfen erarbeitet, und die Rezeptur wurde taxiert.ErgebnisseEs konnte nachgewiesen werden, dass die finale Rezeptur stabil in der Apotheke hergestellt und über 3 Wochen gelagert werden kann. Es haben sich keine Bedenken bezüglich der Verträglichkeit des Rezeptursaftes ergeben. Die physikochemischen Eigenschaften und der Geschmack der Rezeptur ermöglichen den beabsichtigten Gebrauch als gut dosierbaren Saft für Kinder.SchlussfolgerungDie entwickelte Rezeptur entspricht den Anforderungen der Apothekenbetriebsordnung (§ 7 ApBetrO) und ermöglicht eine exakte, körpergewichtsadaptierte Dosierung von oralem Ivermectin bei Kleinkindern. Untersuchungen zur Pharmakokinetik am Menschen bzw. klinische Studien zum Nachweis der Verträglichkeit und/oder Wirksamkeit liegen für die Rezeptur nicht vor.

Development and Validation of a GMP-Compliant High-Pressure Liquid Chromatography Method for the Determination of the Chemical and Radiochemical Purity of [18F]PSMA-1007, a PET Tracer for the Imaging of Prostate Cancer.

For the PET imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. [18F]PSMA-1007, a radiopharmaceutical labeled with fluorine-18, has excellent properties for the detection of prostate cancer. Essential for the human use of a radiotracer is its production and quality control under GMP-compliance. For this purpose, all analytical methods have to be validated. [18F]PSMA-1007 is easily radiosynthesized in a one-step procedure and isolated using solid phase extraction (SPE) cartridges followed by formulation of a buffered injection solution and for the determination of its chemical and radiochemical purity a robust, fast and reliable quality control method using radio-HPLC is necessary. After development and optimizations overcoming problems in reproducibility, the here described radio-HPLC method fulfills all acceptance criteria—for e.g., specificity, linearity, and accuracy—and is therefore well suited for the routine quality control of [18F]PSMA-1007 before release of the radiopharmaceutical. Recently a European Pharmacopeia monograph for [18F]PSMA-1007 was published suggesting a different radio-HPLC method for the determination of its chemical and radiochemical purity. Since the here described method has certain advantages, not least of all easier technical implementation, it can be an attractive alternative to the monograph method. The here described method was successfully validated on several radio-HPLC systems in our lab and used for the analysis of more than 60 batches of [18F]PSMA-1007. Using this method, the chemical and radiochemical purity of [18F]PSMA-1007 can routinely be evaluated assuring patient safety.

Effect of Different Carriers on In Vitro and In Vivo Drug Release Behavior of Aceclofenac Proniosomes.

Improved bioavailability of Aceclofenac (ACE) may be achieved through proniosomes, which are considered as one of the most effective drug delivery systems and are expected to represent a valuable approach for the development of better oral dosage form as compared to the existing product. However, the carrier in this system plays a vital role in controlling the drug release and modulating drug dissolution. Accordingly, a comparative study on different carriers can give a clear idea about the selection of carriers to prepare ACE proniosomes. This study aims to evaluate the role of maltodextrin, glucose, and mannitol as carriers for in vitro and in vivo performance of Aceclofenac (ACE) proniosomes. Three formulations of proniosomes were prepared by the slurry method using the 100 mg ACE, 500 mg span 60, 250 mg cholesterol with 1300mg of different carriers, i.e., glucose (FN1), maltodextrin (FN2), and mannitol (FN3). In vitro drug release studies were conducted by the USP paddle method, while in vivo studies were performed in albino rats. Pure ACE was used as a reference in all the tests. Lastly, the results were analyzed using the High-Pressure Liquid Chromatography (HPLC) method, and data were evaluated using further kinetic and statistical tools. No significant differences (p > 0.05) in entrapment efficiency (%EE) of FN1, FN2, and FN3 (82 ± 0.5%, 84 ± 0.66%, and 84 ± 0.34% respectively) were observed and formulations were used for further in vitro and in vivo evaluations. During in vitro drug release studies, the dissolved drug was found to be 42% for the pure drug, while 70%, 17%, and 30% for FN1, FN2, and FN3, respectively, at 15 min. After 24 hrs, the pure drug showed a maximum of 50% release while 94%, 80%, and 79% drug release were observed after 24 hr for FN1, FN2, and FN3, respectively. The in vivo study conducted on albino rats showed a higher Cmax and AUC of FN1 and FN2 in comparison with the pure ACE. Moreover, the relative oral bioavailability of proniosomes with maltodextrin and glucose as carriers compared to the pure drug was 183% and 112%, respectively. Mannitol- based formulation exhibited low bioavailability (53.7%) that may be attributed to its osmotic behavior. These findings confirm that a carrier plays a significant role in determining in vitro and in vivo performance of proniosomes and careful selection of carrier is an important aspect of proniosomes optimization.

Determination of polycyclic aromatic hydrocarbon metabolites in urine of coke oven workers in Turkey and exposure assessment

Coke-oven workers are occupationally exposed to high concentrations of polycyclic aromatic hydrocarbons. In this study, 1-hydroxypyrene, 9-hydroxyphenantrene, and 3-hydroxybenzo[a]pyrene levels were determined in the urine of occupationally exposed coke-oven worker as markers of exposure to polycyclic aromatic hydrocarbons. The validated high-pressure liquid chromatography method with fluorescence detection was performed for metabolite analysis. Average values of 1-hydroxypyrene were 1.26 µmol/mol creatinine and of 9-hydroxyphenantrene 3.68 µmol/mol creatinine in the workers group, and 0.04 and 0.06 µmol/mol creatinine in the control group. While the average value of 3-hydroxybenzo[a]pyrene was 0.007 µmol/mol creatinine in the workers group, it was below the limit of detection in the control group. All of the mean 1-hydroxypyrene values (coke-oven workers overall mean = 1.26 μmol/mol creatinine; high exposure group mean = 1.91 μmol/mol creatinine; low exposure group mean = 0.66 μmol/mol creatinine) obtained in the workers group were higher than the biological exposure index (0.5 μmol/mol creatinine) that warrants occupational exposure proposed by American Conference of Government Industrial Hygienists. Urinary 1-hydroxypyrene mean levels of all coke-oven workers and the high exposure group exceeded the no observed genotoxic effect level of 1 μmol/mol creatinine.