Pharmaceutical Bulk Research Articles

Method development and validation of an analytical quality by design ultrafast liquid chromatographic method for the determination of bedaquiline from pharmaceutical bulk and nanoemulsions.

Bedaquiline (BDQ) is a drug used to treat multidrug-resistant tuberculosis (MDR-TB). It exhibits exposure-dependent efficacy in eliminating Mycobacterium tuberculosis (Mtb). An easy, efficient and precise reverse-phase ultrafast liquid chromatography (RP-UFLC) method was developed to validate the free base of the antitubercular medication BDQ. BDQ was separated using a 10:90 v/v mobile phase of ammonium acetate buffer solution (pH = 5.4) and high-performance liquid chromatography-grade methanol, with a flow rate of 1.5mL/min and a UV detection wavelength of 226 nm. By using the Box-Behnken design (BBD) and response surface methodology (RSM), the method was optimised by varying critical analytical attributes (CAA) and critical performance attributes (CPAs) namely ammonium acetate fraction (%), flow rate (ml/min), buffer system molarity (M) and pH. BDQ was eluted at 7.5min utilising isocratic elution. The method was linear in the concentration range of 0.5-300 μg/mL with limit of detection values of 0.039 μg/mL and limit of quantification of 0.12 μg/mL. The results indicate that this validated method can be used as an alternative method for assay of BDQ.

Development and Validation of UV-visible Spectrophotometry Method for Simultaneous Estimation of Rutin and Curcumin in Bulk Pharmaceuticals

Development and Validation of UV-visible Spectrophotometry Method for Simultaneous Estimation of Rutin and Curcumin in Bulk Pharmaceuticals

Development of Two Eco-Friendly and High-Throughput Microwell Spectrophotometric Methods for Analysis of an Antibacterial Drug Tulathromycin in Pharmaceutical Bulk Form.

Tulathromycin (TUL) is a triamilide antibacterial drug which has been approved for use in the European Union and the United States for the treatment and prevention of bovine respiratory diseases. The existing methods for determination of TUL in its pharmaceutical bulk form are very limited and suffer from major drawbacks. The aim of this study was the development of two innovative microwell spectrophotometric methods (MW-SPMs) for determination of TUL in its pharmaceutical bulk form. The formation of charge-transfer complexes (CTCs) of TUL, as an electron donor, was investigated with 2,5-dihydroxy-3,6-dichlorocyclohexa-2,5-diene-1,4-dione (HCD) and 2,3-dichloro-5,6-dicyano-p-benzoquinone (CBQ), as π-electron acceptors. The CTCs were characterized using UV-Vis spectrophotometry and computational calculations. The reactions were employed for the development of two MW-SPMs with one step for the quantitative analysis of TUL. The formation of CTCs was confirmed via the formation of characteristic absorption bands with maximum absorption at 520 and 460 nm for CTCs with HCD and CBQ, respectively. The stoichiometry of both CTCs was found to be 1:1, and the values of different spectroscopic and electronic constants confirmed the stability of the CTCs. The mechanisms of the reactions were postulated. The linear range of both MW-SPMs was 10-500 µg/mL. The LOQs were 13.5 and 26.4 µg/mL for methods involving reactions with HCD and CBQ, respectively. Both methods were successfully applied to the quantitation of TUL in pharmaceutical bulk form with acceptable accuracy and precision. The results of eco-friendliness/greenness assessment proved that both MW-SPMs fulfill the requirements of green analytical approaches. In addition, the one-step reactions and simultaneous handling of a large number of samples with micro-volumes in the proposed methods gave them the advantage of high-throughput analysis. This study described two new MW-SPMs as valuable analytical tools for the determination of TUL. The proposed methods are valuable analytical tool for the analysis of bulk form of TUL.

A Review on The Impurity Profile of Pharmaceuticals

A collection of analytical procedures known collectively as “impurity profiling” are intended to detect, identify, clarify the structure of, and quantify both organic and inorganic impurities as well as residual solvents in pharmaceutical formulations and bulk pharmaceuticals. This is the main task of contemporary drug analysis since it is the most effective approach to describe the stability and quality of pharmaceutical formulations and bulk pharmaceuticals. To keep an eye on them, specific analytical techniques must be created. When modifications are made to the synthesis, formulation, or production processes, even if they are done to improve them, new purities could be seen. The identification of impurities in Active Pharmaceutical Ingredients (APIs) and the need for purity are being emphasised by a number of regulatory bodies, including the Canadian Drug and Health Agency (CDHA), the United States Food and Drug Administration (FDA), and the International Conference on Harmonisation (ICH). Pharmaceutical products can contain impurities from a variety of sources, including reagents, heavy metals, ligands, catalysts and other materials like charcoal, filter aids, and the like. Degraded end products from hydrolysis, photolytic cleavage, oxidative degradation, decarboxylation, and other processes can also contain impurities, as can enantiomeric impurities. The various pharmacopoeias, including the Indian, American, and British pharmacopoeias, are gradually adding restrictions to the permissible concentrations of contaminants found in APIs or formulations. Capillary electrophoresis, electron paramagnetic resonance, gas-liquid chromatography, gravimetric analysis, high performance liquid chromatography, solidphase extraction techniques, liquid-liquid extraction techniques, mass spectrometry, ultraviolet spectrometry, infrared spectroscopy, supercritical fluid extraction column chromatography, nuclear magnetic resonance (NMR) spectroscopy, and RAMAN spectroscopy are some of the techniques used to isolate and characterize impurities in pharmaceuticals. Liquid Chromatography (LC)-Mass Spectroscopy (MS), GC-MS, LC-NMR, LC- NMR-MS, and LC-MS are the most frequently used hyphenated techniques for drug impurity profiling. This demonstrates the importance and range of drug impurity profiling in pharmaceutical research.

Development and Validation of an Innovative Stability Indicating Method Using UVSpectroscopy Techniques for Ritonavir in Bulk Drug and Pharmaceutical Dosage Forms

Ritonavir is a protease inhibitor used to treat HIV/AIDS. It is seldom employed for its antiviral activity but instead as a booster for other protease inhibitors. Our study's significant objective is to develop a new, simple, accurate, precise, and reproducible UV spectrophotometric approach for investigation by apotheosis to analyze ritonavir. Three alternative simple, accurate, and precise UV spectrophotometric techniques-the, zero-order (method A), first-order (method B), and the area under the curve (method C) spectrophotometric methods have been established for the measurement of ritonavir in bulk and pharmaceutical dosage. The drug was dissolved in ethanol, and then 0.063 M Phosphate buffer solution (pH 7.0), and the observed λmax are 271 nm for the zero-order spectrophotometric method (method A), 258 nm for the first-order spectrophotometric method, 260–281 nm for the area under the curve spectrophotometric method (method C). Under the optimum conditions, linear relationships with good correlation coefficients 0.9994–0.9999 were found between the reading and the corresponding concentration of the drug in the range of 10-50 μg/ml. The proposed methods can detect the analyte in the lower limits of 0.24 to 0.38 μg/ml. The precision of the methods was satisfactory, and the percentage relative standard deviation values did not exceed 2%. The proposed methods were successfully applied to the analysis of ritonavir in its bulk and commercial formulations with good repeatability and reproducibility; the label claim percentages ranged from 99.56 to 99.64 ± (0.34-0.63) % w/v. The research findings of the current approach were shown to be more accurate and trustworthy for ritonavir in pharmaceutical dosage forms and bulk pharmaceuticals compared to those previously reported by the spectrophotometric approaches. The proposed techniques can be used for routine inspections without causing any interference from excipients or other substances because of the quick and repeatable analysis.

An empirical assessment of the impact and role of the indenting agents in the supply chain of pharmaceutical raw material from China

Even though India ranks third in the world for pharmaceutical output, there is an undue reliance on China for APIs (Active Pharmaceutical Ingredients), bulk pharmaceuticals, intermediates, primary raw materials, and fermentation technology. Only Chinese raw materials are used in the nation’s production of pharmaceutical raw materials. The Export Promotion Council for Pharmaceuticals is taking steps to reduce this undue reliance on China. If China elected not to provide those products, it would have problems addressing both domestic health needs and export requests. India must act to create a production process strategy since China’s costs are gradually growing. The Pharmaceuticals Export Promotion Council also represents these issues in the relevant fora, and the Center takes the condition into consideration. To accomplish these goals, the researcher in this paper is attempting to determine the impact of the indenting agent’s position in the supply chain between Chinese manufacturers and end-users during the import of pharmaceutical raw materials. China still has a more important role to play, though. To identify the variables and accomplish the research’s goals, analysis of variance methodologies was employed and 118 end consumers from various regions of India were recruited.

A NEW STABILITY INDICATING UPLC METHOD FOR THE DETERMINATION OF TWO ANTIDIABETIC DRUGS IN COMBINATION: APPLICATIONS TO BULK AND TABLET FORMULATION

Objective: This work was intended to develop a rapid and sensitive stability-indicating ultra-performance liquid chromatographic (UPLC) method for the determination of Metformin and Gliclazide simultaneously in their pharmaceutical bulk and tablet formulation. Methods: Separation was performed on Lunna C18 (100 mm x 2.6 mm, 1.6µ) column by using trifluoroacetic acid buffer: acetonitrile (70: 30, v/v) as a mobile phase at a flow rate of 1 ml/min and a wavelength of detection of 227 nm. Method validation and forced degradation studies were conducted per the respective guidelines of the International Conference on Harmonization. Results: Retention times under the optimized condition were 1.719 min and 2.845 min for Metformin and Gliclazide, respectively. Linearity ranged between 25.0-375.0 µg/ml for Metformin and 4.0-60.0 µg/ml for Gliclazide with a coefficient of determinations (r2) of greater than 0.99. The limit of detection values was 0.25 µg/ml for Metformin and 0.04 µg/ml for Gliclazide. Recovery results ranged from 99.63-101.23 %, and the % RSDs for the precision studies were less than 1.11% for both drugs. The % degradations at various stress conditions ranged from 14.0-5.0% for Metformin and 13.3-2.4% for Gliclazide. The analyte peaks were clearly resolved from the degradant peaks in forced degradation studies. Conclusion: A fast, sensitive and efficient ultra-performance liquid chromatographic method was successfully developed and validated for the concurrent estimation of Metformin and Gliclazide in their combination, and thus the proposed method can be effectively applied for routine quality control works.

RP-HPLC Method Development and Validation for the Estimation of Chlordiazepoxide in Novel Excipient Containing Formulations

An effort has been made to establish a simple and exact reverse-phase HPLC technique for the analysis of Chlordiazepoxide in bulk medication and formulations. A Phenomenex Luna C18 stationary phase (250 4.6 mm, 5) and dipotassium hydrogen phosphate anhydrous buffer (pH 6.8) and acetonitrile in an isocratic mode were employed in this method's present development. Following the ICH recommendations, many aspects such as linearity range, system applicability and accuracy and precision were examined. The LOD and LOQ were also evaluated. Robustness and solution stability were also examined. Chlordiazepoxide concentrations in a new formulation comprising an excipient were successfully measured using the newly designed and validated technique. When using the approach, the recovery rate was determined to be between 99.00 percent and 101.00 percent. Detection and quantification of Chlordiazepoxide in pharmaceutical formulations were shown to be possible using this method (99.7 percent). Methods for rapid screening of Chlordiazepoxide in bulk pharmaceuticals and formulations were developed using an RP-HPLC technology that is both linear and robust.

NEW VALIDATED STABILITY-INDICATING RP-HPLC METHOD FOR THE SIMULTANEOUS DETERMINATION OF METFORMIN HYDROCHLORIDE, LINAGLIPTIN AND EMPAGLIFLOZIN IN BULK AND PHARMACEUTICAL DOSAGE FORMS

Objective: The purpose of the present study is to develop simple, fast, accurate, precise, and robust stability-indicating reverse phase high-performance liquid chromatographic (RP-HPLC) method for the simultaneous determination of metformin HCl, empagliflozin, and linagliptin in their combinations. Methods: Separation was performed on Agilent Eclipse XDB-C18 (250 mm x 4.6 mm, 5 µm) column with a mobile phase consisting of 0.1 % triethylamine (pH =3) buffer and acetonitrile in the ratio 40: 60 (v/v) at a flow rate of 1 ml/min. Detection of the analytes was carried out at a wavelength of 240 nm with a photodiode array detector. The developed method was validated as per the International Conference on Harmonization (ICH) guidelines. Results: The retention time values under the optimized condition were 2.660 min, 3.586 min, and 5.412 min for metformin HCl, linagliptin, and empagliflozin, respectively. The method was linear over a concentration range of 100 µg/ml-1500 µg/ml, 0.5 µg/ml-7.5 µg/ml, and 2.5 µg/ml-37.5 µg/ml for metformin HCl,linagliptin and empagliflozin respectively. The limit of detection (LOD) of the method was found to be 4.00 µg/ml, 0.02 µg/ml, and 1.00 µg/ml for metformin HCl, linagliptin, and empagliflozin, respectively. The degradation peaks were clearly resolved from the parent drug peaks in the chromatograms of forced degradation studies. Conclusion: The validated method was successfully applied for the determination of metformin HCl, linagliptin, and empagliflozin in their combined tablet dosage forms and hence can be used for the routine quality control of the drugs in pharmaceutical bulk, and dosage forms.

MODERN INSTRUMENTAL METHODS FOR QUALITATIVE AND QUANTITATIVE ANALYSIS OF LAPATINIB IN BIOLOGICAL FLUIDS AND DOSAGE FORMS (REVIEW)

Lapatinib is a small molecule, a heterocyclic quinazoline derivative. The drug is used for targeted therapy of patients with breast cancer, in which there is overexpression of the human epidermal growth factor receptors (HER/ErbB). This review is devoted to studying modern instrumental methods of qualitative and quantitative analysis of lapatinib, which can be used both for quality control and standardization (of bulk pharmaceuticals and dosage forms) and pharmacokinetics studies of a drug. Reverse-phase high-performance liquid chromatography (RP-HPLC) is mainly used to identify lapatinib in tablets. Depending on the purpose of the study, various detectors are used (ultraviolet or diode-matrix detector), which makes it possible to determine not only the native compound but also the products of its degradation. Definition of lapatinib in the presence of degraded products is necessary for forced degradation studies to determine drug stability. When a drug is being developed, it is important to define and understand its pharmacokinetics. For such studies, high-performance liquid chromatography (HPLC) coupled with the mass selective detector is often used. It allows determining lapatinib in biological fluids. However, these methods are not applicable for identifying the drug directly in dosage forms and require further development and validation.

Impact of Patent (Amendment) Act, 2005 on Indian Pharmaceutical Industry

Since 1901, the Indian pharmaceutical industries have expanded and strengthened to become a significant supplier of healthcare items, meeting around 90% of the nation’s need for bulk pharmaceuticals, drugs intermediates, chemicals for the medicinal base, pharmaceutical compounds, medicinal formulas, drugs, tablets, orals, respules/capsules, and injectables. Indian pharmaceutical industry has embarked not only on national markets but it has an esteemed and illustrious position in international markets also. India is the world’s third-largest pharmaceutical manufacturer by volume and fourteenth-largest by value. The growth and empowerment of the pharmaceutical industry is totally attributed to the rules and principles governing the operations and evolution of the pharmaceutical industry in India. These rules are the controlling guidelines mandated by the Government of India, through the Acts and amendments made in the acts at various times. One of the major and most influential amendment is the Patent (Amendment) Act, 2005. This act has provided new dimensions and horizons to the Indian pharmaceutical industry and a good number or rational researches have been performed on this subject. It has thus been a fascination to dig the researcher’s points of views about how The Patent (Amendment) Act, 2005 after TRIPS has impacted the Indian pharmaceutical industry since this act has been passed. This survey paper is an attempt to bring out the deviations and modifications, Indian pharmaceutical industry has been gone through, since year 2005.

Regulatory requirements for verification of sampling plan for solid pharmaceutical bulk product

The most convenient sampling plan for routine testing at batch release for a solid pharmaceutical bulk product is a sampling plan with requirements for generating a composite sample. Verification is required before such a sampling plan can be used for routine testing. The verification needs to demonstrate that the composite sample is representative of the whole batch and is considering the most stressed part of the manufacturing process of the solid pharmaceutical bulk product. As part of verification, increased sampling should be performed to demonstrate that the manufacturing process yields a homogeneous product. The sampling for batch release testing of a solid pharmaceutical bulk product is performed at the end of the production process from each individual container where the batch is stored. All containers combined represent the variability of the entire batch, that is, the individual samples taken from each container. The verification process should demonstrate that individual samples taken from each container gives comparable sampling variability as a composite sample is prepared from all containers. A statistical evaluation and comparison of the results from individual samples and composite sample is most appropriate when performed by using Equivalence Test (TOST). If such equivalence is obtained between individual samples from each container and a composite sample, then it is possible to limit the routine testing to representative composite samples from predetermined containers defined in the sampling scheme. The sampling plan with a representative composite sample should be verified enough that it is suitable for all future batches. Keywords: Pharmaceutical sampling, solid pharmaceutical bulk product, representative composite sample, verification of sampling plan with composite sample, Equivalence Test (TOST)

Full evaporation headspace gas chromatography with thermal conductivity detection for the direct determination of water in solid pharmaceutical bulk products

Headspace gas chromatography (HS-GC) has the potential to be used for water determination in pharmaceutical products. In this article, its use for the determination of water in solid samples is explored without the need of dissolution by means of the full evaporation technique (FET). This way, water is thermally removed from a small amount of sample which is directly weighed in the vial. This simplifies considerably the method since no diluent has to be searched and HS saturation is avoided. Blank corrections were performed to compensate for atmospheric moisture variation. Moreover, the performance of mass spectrometry (MS) and thermal conductivity detection (TCD) was compared. The method showed excellent figures of merit when working with TCD, such as R2> 0.99 and RSD< 5% for each level of the calibration curve. Eight samples were carefully studied at different equilibration temperatures to find the optimal working conditions for each case and the results were compared to the ones obtained by Karl Fischer titration (KFT). Both methods showed restrictions and proper case by case optimization/validation turned out to be mandatory. Hyphenation with a flame ionization detector (FID) in series with the TCD showed the benefit to be useful for testing residual solvents (RS) simultaneously.

The Validation and Development of Analytical Technique for the Fast and Economical Evaluation of Amoxicillin in Solid Dosage form Through UV/Visible Spectroscopy

Objective: The key objective of the study is to explore the sensitive, rapid, simple, accurate and economic UV/Vis spectrophotometric method to determine the amount of Amoxicillin trihydrate (AMTR) in bulk pharmaceuticals and in various formulations including dry powder (syrup), tablets and capsules by employing Copper sulphate buffer solution.&#x0D; Methodology: The current spectroscopic analysis performed with 12.5 μg/ml concentration of AMTR at 320 nm follows the Beer’s Lambert Law. The linearity range (10-15µg/ml) and regression data presented a significant correlation coefficient (r2 =0.999). The appropriate level of accuracy, precision, linearity, and mean percentage recovery of AMTR were found adequate relating to the % age error and standard deviations.&#x0D; Results: Amoxicillin trihydrate and its known strengths were scanned and analyzed by our validated method such as; 10.0 µg/ml Amoxicillin (80%), 11.25 µg/ml Amoxicillin (90%), 12.5 µg/ml Amoxicillin (100%), 13.75 µg/ml Amoxicillin (110%) and 15.0 µg/ml Amoxicillin (120%).&#x0D; Conclusions: As the recommended protocol of amoxicillin determination (spectrophotometry) is accurate, precise and statistically evaluated, therefore it could readily be employed for qualitative purposes of either for the raw material and pharmaceutical preparations.

Method Development and Validation of RP-HPLC method for Saxagliptin and Sitagliptin in Pharmaceutical Dosage Form - A Review

The study's goal was to develop a plain, quick, and responsive RP-HPLC method for determining the concentrations of Saxagliptin and Sitagliptin in pharmaceutical bulk dosage form (bulk powders). Isocratic elution with Cosmosil C18 (250nm 4.6nm, 5m particle size) and UV detection at 212nm for Saxagliptin and Develosil ODS HG-5 RP-C18 (15cm 4.6mm, 5m particle size) and UV detection at 255nm for Sitagliptin were used in this chromatographic process. Methanol and water (70:30) in a mobile solution with a flow rate of 0.8ml/min for Saxagliptin and (0.05m) phosphate buffer: methanol and water (70:30) in a mobile solution with a flow rate of 0.8ml/min for Saxagliptin and (0.05m) phosphate buffer: These protocols have been put through their paces in accordance with ICH guidelines. The normal curves for Saxagliptin and Sitagliptin were observed to have a linear relationship across the analytical ranges of 10-50 g/ml and 30-70 g/ml, respectively. The accuracy, precision, limit of identification, the limit of quantification, and robustness of the system were all calculated. Various analytical methods such as UPLC (Ultra performance liquid chromatography), UV spectroscopy, LC-UV methods have performed to the quantitative determination of Saxagliptin and Sitagliptin drugs.

HPLC-UV Method Development and Validation for Sulfadoxine from its Potential Interfering Impurities

Objective: To address the separation of interfering potential impurities associated with the drug is always a daunting task. We present the method validation and quantitative determination of sulfadoxine (SUL), an anti-malarial drug with the most important interfering impurities present in pharmaceutical dosages and bulk samples using HPLC-UV method. Methods: The UV detection was obtained at 270 nm and SUL is separated on Sunfire C18 (25 cm x 4.6 mm x 5 μm) column at 45°C with a flow rate of 1.0 mL/min in a mobile phase (CH3COOH: CH3CN). The stress testing (acidic/basic/oxidative) was performed using HPLC for SUL and its impurities, showing the highly efficient separation peaks between degradant and drug products. Results: The developed method was found to be highly accurate and sensitive in regulation with ICH guidelines. Also, it was found to be free from interference from degradation products which allows the stability indicating capability of developed HPLC-UV method for SUL for validation in bulk drugs. Conclusion: The main advantages of the present method; (a) Separation achieved in 30 minutes, (b) MS compatible mobile phase renders this developed method can be directly adapted to LC-MS without any major modifications in the near future, and (c) separation of twelve impurities on Sunfire C18 column. The CFs (correction factors) had been calculated for all the impurities. It was found to be 1.6 (IMP IX), 1.70 (IMP XI) and in between 0.8-1.3 for all other impurities. The LOD of the developed method for all the analytes was in the range of 0.05 to 0.11 μg/mL and the LOQ values were in the range of 0.17 to 0.36 μg/mL.

GREEN SYNTHESIS OF SILVER NANOPARTICLES, METHOD DEVELOPMENT AND VALIDATION BY UV SPECTROSCOPY IN BULK PHARMACEUTICALS

The silver nanoparticle is an antibacterial, nontoxic agent. Its conventional synthesis usually generates toxic waste while reaction proceeds hence, green synthesis approach is used have for synthesis of silver nanoparticles (Ag-NPs) by using Datura metel leaf extract as reducing agent. The colour change from colourless to brown was the visual identification for formation of Ag-NPs and showed absorption at 447 nm. The Ag-NPs were of size 180 nm analysed by SEM and characterised by FTIR, where carboxylic peak was obtained at 1569 cm-1, besides confirming presence of alcoholic group and polyphenols. Further, validated method was developed and linearity was found to be 0.995 and % RSD of validation parameters was found to be within the limit &lt;2%. A simple, lab scale, rapid, accurate, precise and sensitive spectroscopic method has been developed and validated as per ICH guideline for synthesized Ag-NPs in bulk pharmaceuticals by UV vis spectrophotoscopy and it is applicable for routine analysis.

Technological Innovations and their Impact on Pharmaceutical Industry: An Empirical Study of Medical Representatives

The pharmaceutical industry's unique company model and commercial operations have a notable impact on the process of delivering new drugs to patients, even though they are not widely comprehended outside of the industry. The likelihood of a new drug succeeding could be higher, and the process is very time-consuming, costly, and hazardous. After implementing international patent rules on January 1st, 2005, the Indian Pharmaceutical Industry saw a tremendous shift. India's indigenous pharmaceutical businesses have seen massive growth in R &amp; D investment to remain competitive in the global pharmaceutical industry. India has very well researchers, a well-established computer industry, and technology for producing bulk pharmaceuticals and formulations, despite the country's limited pharmaceutical market and lack of financing for drug development initiatives. Following a discussion of the company's commercial realities and restrictions, along with its current issues, there follows an examination of some of the expected future commercial and technological advances in the company.

Method Development and Validation of Irbesartan by RP-HPLC Method

This study includes development of RP-HPLC method for estimation of Irbesartan. The developed method was validated as per ICH guidelines in terms of specificity, accuracy, linearity, LOD, LOQ, ruggedness and robustness. The assay experiment showed that the contents of Irbesartan estimated in the tablet dosage were free from interference of excipients, which indicate that developed method was specific. Recovery of standard added drugs was found to be 97.2–99.9% for Irbesartan indicating that the proposed method was accurate. After performing analysis by different analyst; it was found that the RP-HPLC method for the determination of Irbesartan % RSD of ruggedness for standard 0.0425% and tablet 0.0142% was found to be rugged. % RSD of robustness was well within the limits for standard 0.36% and tablet 1.87% that the proposed method was robust. The LOD was 0.074 μg/ml for standard drug of Irbesartan. For standard drug of Irbesartan the LOQ were found to be 0.24 μg/ml This demonstrated that the developed RP-HPLC method was simple, linear, precise, accurate, robust and rugged, could be conveniently adopted for the routine quality control analysis of Irbesartan from it's pharmaceutical dosage form and bulk drug.

Phosphate Binders Derived from Natural Ores Contain Many Kinds of Metallic Elements Besides Their Active Ingredient Metals.

Most patients undergoing dialysis are required to take many phosphate binder pills to control hyperphosphatemia. Phosphate binders prescribed in Japan are classified into two types: metal-based binders (Ca carbonate, lanthanum carbonate, ferric citrate hydrate, and sucroferric oxyhydroxide) and chemically synthesized polymers (sevelamer hydrochloride and bixalomer). The raw materials of metal-based phosphate binders are natural ores; thus, such binders may contain several other metallic elements. We measured the elemental contents in six metal-based phosphate binders using an inductively coupled plasma mass - spectrometry (ICP-MS) method. As a result, despite being in small amounts, ore-derived phosphate binders contained various elements besides their active ingredient metals: Na, Mg, P, Mn, Fe, Sr, Y, Ba, La, Nd, and Pb in three Ca-based products; Mg, P, Se, Ce, and Gd in one La-based product; and Na, Mg, Al, P, Ca, Ti, Cr, Mn, Co, Ni, Ge, Ba, and La in two Fe-based products. These elements are considered to have originated from pharmaceutical bulk and from pharmaceutical additives. It is unlikely these elements are immediately harmful to patients. However, it should be emphasized that patients undergoing dialysis do not have a urinary excretion route and are administered many phosphate binder pills every day over a long period of time. In the future, pharmaceutical companies may have to disclose standard amounts and/or analytical values regarding the type and quantity of metallic elements in the final formulation or pharmaceutical bulk derived from natural ores.