Application Finder

Raman spectroscopy is used for material characterization by analyzing molecular or crystal symmetrical vibrations and rotations that are excited by a laser, and exhibit vibrations specific to the molecular bonds and crystal arrangements in the molecules. Raman technology is a valuable tool in distinguishing different polymorphs. Examples of portable Raman spectroscopy for identification of polymorphs and in monitoring the polymorphic transiton of citric acid and its hydrated form are presented.

The NanoRam is able to test material through multiple layers of transparent plastic bags. Postive identification of material on PE bags from 1 to 9 layers were obtained, demonstrating minimum interference from the PE bags on the material identification result.

Metrohm’s ST Raman technology enables fast, contactless identification of substances through opaque packaging, expanding safe, field-ready use of Raman spectroscopy.

Analytical methods to perform CU testing should ideally be fast, noninvasive and achieved with limited sample preparation. Recently, transmission near-infrared (NIR) spectroscopy and transmission Raman spectroscopy have both been explored as alternative methods for rapid and non-destructive on- and at-line CU testing with no sample preparation. Although quick and nondestructive, transmission NIR spectroscopy suffers from poor chemical selectivity and is sensitive to changes in the testing environment. Transmission Raman spectroscopy combined with chemometric modeling is quickly emerging as a valued technique for CU testing due to its high chemical specificity, which is particularly useful when dealing with complex pharmaceutical formulations that contain multiple components.

The two most common mathematical representations used with handheld Raman spectroscopy as decision-making tools for spectroscopic data: Hit Quality Index (HQI) and significance level (p-value) are presented.

This technical note is to demonstrate the NanoRam material identification through dark brown plastic bags. NanoRam is shown to work for material identification inside dark brown polyvinyl bag.

Handheld Raman is used for raw material testing of different sample types and forms. The use of optimized sampling accessories enhances the utility of handheld Raman without compromising data quality or complicating testing.

In this note, we use a model drug, acetaminophen, to demonstrate the capability of QTRam® to quantify low concentrations of API in compressed tablets.QTRam® is a compact transmission Raman analyzer designed specifically for content uniformity analysis of pharmaceuticals in solid dosage forms.

100% starting materials identification testing is one of the FDA’s directives as per 211.84 for FDA regulated industries such as Pharmaceutical, Vaccines, Cosmetics, Tobacco, Animal veterinary products, Food, etc. STRam®-1064 is a Raman analyzer uniquely suited for this purpose. It measures samples through thick packaging materials such as plastics, multilayer kraft paper sacks, and HDPE containers. A long wavelength laser is used to suppress fluorescence. The ID algorithm isolates the sample signature by subtracting that of the packaging material and compares that with library spectra to achieve identification.

By means of azide analysis in Irbesartan a simple, fast, precise and accurate ion chromatographic method for the determination of traces of inorganic contaminants in pharmaceuticals is described. Traces of toxic azides in pharmaceutical products can accurately be determined in the sub-ppb range after Metrohm Inline Matrix Elimination using isocratic ion chromatography (IC) with suppressed conductivity detection. While the azide anions are retained on the preconcentration column, the interfering pharmaceutical matrix is washed away by a transfer solution, ideally consisting of 70% methanol and 30% ultrapure water. The analytical setup provides a well-resolved azide peak and thus alleviates the common drawback of excipient interferences, especially from the nitrate anion. Calibration with azide standards is linear over the range of 5…80 ppb, providing a coefficient of determination of 0.9995. The limit of detection (LOD) and the limit of quantification (LOQ) of azide in Irbesartan are 5 and 30 µg/L respectively; the relative standard deviations (RSD) for the peak area, peak height and retention time being smaller than 3.9%. Robustness testing involved variation of column oven temperature and composition of the transfer solution and, in terms of peak area, provided RSDs smaller than 2.8% and 3.1% respectively.

Benzbromaron is one of the main uricosuric drugs currently used. In addition to sophisticated and expensive LC-MS and GC-MS methods, benzbromaron can be effectively determined by titration with sodium hydroxide solution using a straightforward, fully automated sample preparation method. A high-frequency homogenizer comminutes one or three tablets within 90 or 120 s respectively. The overall analysis time is 8 minutes. Ten-fold determinations with one and three tablets resulted in a benzbromaron content of 99.2 and 98.7 mg per tablet respectively. Increasing the number of tablets from one to three lowers the RSD from 1.36 to 0.88%. These results show an excellent agreement with the benzbromaron content indicated by the manufacturer (approx. 100 mg/tablet).Besides the presented Titrando/homogenizer combination, the other two members of the 815 Robotic Soliprep Sample Processor family offer comprehensive sample preparation possibilities within the fields of IC, HPLC, ICP or voltammetry.

The water content of tablets determines the release of their active ingredients as well as their chemical, physical, microbial and shelf-life properties. Accordingly, the water content is of crucial importance and has to be accurately determined. This paper describes the straightforward determination of the water content using automated volumetric Karl Fischer titration (KFT). Tedious sample preparation steps are eliminated by using a high-frequency homogenizer that additionally serves as a stirrer. Prior to titration, the homogenizer comminutes the tablets directly in the KF solution. As the comminution process takes place directly in the hermetically sealed titration vessels, interference from atmospheric humidity does not occur. Even after 24 h in the vessels, the moisture content of four different tablet type samples was within 93…108% of the initially determined values. With a coefficient of determination of 0.99993 the KF method is highly linear for water amounts between 4 and 215 mg. For all investigated tablet types, KFT provides results that lie within the range expected by the manufacturer.

The analytical challenge treated by the present work consists in detecting sub-ppb concentrations of low-molecular-weight amines in the presence of strongly retained cationic drugs by using ion chromatography (IC) with upstream inline coupled-column matrix elimination (CCME). In contrast to direct-injection IC, where the late elution of strongly retained drugs requires eluents with added acetonitrile, the CCME technique uses two preconcentration columns in series. In an «inverse matrix elimination step, cationic drug and target amines are trapped on a high-capacity and a very-high-capacity preconcentration column, respectively. During amine determination, a rinsing solution flushes the drug to waste. This significantly shortens the analysis time and improves sensitivity as well as selectivity. Besides the determination of monomethylamine in Nebivolol hydrochloride discussed here, the CCME technique is a promising tool for detecting further low-molecular-weight amines in a wide range of drugs.

The 800 Dosino controlled by tiamo™ or Touch Control can be used universally for dosing and liquid handling tasks in both the analytical laboratory or directly in the synthesis laboratory. This poster looks at three typical liquid handling applications, the synthesis of metal-organic compounds, the preparation of standards, and the determination of pharmaceutical ingredients.

The poster describes the water determination in pharmaceuticals using the Karl Fischer oven technique.

This poster describes a method for automated and precise dosing of liquid samples into the Karl Fischer titration cell using Metrohm Dosino liquid handling technology. First, the titer was automatically determined with ultrapure water. The same dosing procedure proved valuable for the automated water determination in highly viscous water-glycol fluids and low-boiling organic solvents such as n-pentane. Lastly, the method copes with the labor-intensive and human error-prone suitability test stipulated in chapter 2.5.12 in the European Pharmacopoeia.

Pharmaceutical analysis guarantees drug safety by providing information on the identity, content, quality, purity, and stability of pharmaceutical products using analytical chemistry. Ion chromatography (IC) offers a broad range of pharmacopeia-compliant applications for quality control, monitoring, and improving drug manufacturing.As a very accurate and versatile technique, IC meets the requirements of many pharmaceutical applications. IC is a USP-accepted standard method for the determination of active pharmaceutical ingredients (APIs), excipients, impurities,pharmaceutical solutions as well as pharmaceutical starting materials, finished pharmaceutical products (FPPs) and even body fluids.This poster describes some typical examples.

This poster presented jointly with USP at AAPS meeting shows, that we successfully developed and validated a single IC procedure for potassium assay and identification in potassium bicarbonate and potassium chloride for effervescent oral suspension. The optimized chromatographic conditions could be used for other cationic impurities, such as magnesium, calcium, sodium, and ammonium in potassium bicarbonate and potassium chloride for effervescent oral suspension. Single chromatographic method for assay and identification simplifies the overall QA/QC workflow.

This poster presented jointly with USP at AAPS meeting shows, that we successfully validated an IC method to determine chloride and sulfate in drug substances, potassium bicarbonate and potassium carbonate. The proposed IC method overcomes limitations of the turbidimetry/visual comparison methods.

This Bulletin describes a simple polarographic method for the determination of quinine in drinks and tablets. Whereas in drinks quinine can be determined directly, in the case of tablets it must first be extracted. The limit of quantification is 0.2 mg/L or 4 μg/tablet.

Potassium is one of the most common elements and can be found in many different minerals and other potassium compounds. It is of importance for humans, animals and plants as it is an essential mineral nutrient and involved in many cellular functions like cell metabolism and cell growth. For these reasons, it is important to be able to declare the potassium content of food or soil to reduce problems that may arise by a potassium deficiency or extensive consumption.This bulletin describes an alternative to flame photometric method using an ion selective electrode and direct measurement or standard addition technique. Several potassium determinations in different matrices using the combined potassium ion-selective electrode (ISE) are presented here. Additionally, general hints, tips and tricks for best measurement practice are given.

This Application Bulletins describes the determination of nicotinamide (vitamin PP), a vitamin of the B series. Instructions for the determination in solutions (e.g. fruit juice), vitamin capsules and multivitamin tablets are given. The linearity range of the determination is also specified. The limit of detection is approximately 50 μg/L nicotinamide.

This Application Bulletin describes the polarographic determination of folic acid, a vitamin of the B series, also known as vitamin B9 or vitamin BC. Instructions for the determination in solutions (e.g. fruit juice), vitamin capsules and multivitamin tablets are given. The linear range of the determination is also specified. The limit of detection is approx. 75 µg/L folic acid.

This Application Bulletins describes the polarographic determination of thiamine (vitamin B1). The procedure allows an analysis in monovitamin preparations. The linear range of the determination is also given. The limit of detection is approx. 50 µg/L thiamine.

This Application Bulletin describes the polarographic determination of riboflavin (vitamin B2). The procedure allows an analysis in monovitamin preparations. The limit of determination is approx. 100 μg/L.

This Application Bulletins describes the polarographic determination of pyridoxine (vitamin B6). The method given allows determination in monovitamin and in some multivitamin preparations. The linear range of the analysis is also specified. The limit of detection is approx. 100 µg/L pyridoxine · HCI.

Diazepam belongs to the 1,4-benzodiazepine group of compounds, which are used for medical purposes as tranquilizers and antidepressants. This Bulletin describes the determination of diazepam in tablets and body fluids (blood, serum, urine) by means of differential pulse polarography. If a Britton-Robinson buffer pH = 2.8 with a methanol volume fraction of 20% is used as the supporting electrolyte then a pronounced reduction peak is obtained at -0.73 V; this allows diazepam concentrations even below 0.05 µg/mL to be determined in blood. The necessary sample preparation steps are also dealt with in this Bulletin.

Generally speaking, the gas extraction or oven method can be used for all samples which release their water when they are heated up. The oven method is indispensable in cases in which the direct volumetric or coulometric Karl Fischer titration is not possible, either because the sample contains disruptive components or because the consistency of the sample makes it very difficult or even impossible to transfer it into the titration vessel.The present Application Bulletin describes automatic water content determination with the aid of the oven technique and coulometric KF titration, using samples from the food, plastic, pharmaceutical and petrochemical industry.

This Application Bulletin describes the method of near-infrared spectroscopy in diffuse reflection for the purpose of determining residual moisture in a lyophilized pharmaceutical product. Numerous sample vials containing freeze-dried pharmaceuticals were spiked with varying amounts of water for calibration purposes. The resulting differences in the absorption wavelengths of the OH-oscillation were correlated with the water content determined by Karl Fischer titration using the algorithm of multiple linear regression (MLR).

The present Application Bulletin contains NIR applications and feasibility studies using NIRSystems devices in the pharmaceutical industry. Qualitative and quantitative analyses of a wide variety of samples are part of this bulletin. Each application describes the instrument that was originally used for the analysis, as well as the system recommended for the analysis and the results that were achieved thereby.

This Application Bulletin compares the unique focusing technology of the portable Metrohm Raman system "Mira" with conventional methods. The method described here is called Orbital Raster Scan (ORS). Experiments show the advantages of ORS technology, using determination and quantification of medicines as an example. It improves the reproducibility of the Raman signals from targeted, active, pharmaceutical ingredients (APIs) in effervescent, cold medicines. Shorter analysis times and an improved, consistent assignment of spectra of the known medicine with the help of a spectral library are further advantages of ORS technology.

Determination of trans-4-methylcyclohexylamine in a pharmaceutical product using cation chromatography with direct conductivity detection.

Determination of tributylamine in a pharmaceutical product (gabapentine) using cation chromatography with direct conductivity detection.

Determination of Bethanechol chloride and calcium in tablets using cation chromatography with direct conductivity detection.

Determination of Bethanechol Chloride and HPTA (2-hydroxy-propyl-trimethyl ammonium chloride) besides sodium and calcium using cation chromatography with direct conductivity detection.

Determination of benzylamine in a beta blocker (Nebivolol) using cation chromatography with direct conductivity detection. A step gradient for fast elution of the main component is applied.

Determination of dimethylamine in Metformin (N,N-dimethylimidodicarbonimidic diamide, anti-diabetic drug) using cation chromatography with direct conductivity detection.

Bethanechol is a pharmaceutical compound which is used to treat urinary retention. This API (active pharmaceutical ingredient) can be determined by cation chromatography with direct conductivity detection. A good separation is achieved between bethanechol and its degradation product 2-hydroxy-propyl-trimethyl ammonium (HPTA) and the standard cations. Peak shape and resolution meet the USP requirements for bethanechol.

Within the scope of the USP monograph modernization, potassium is determined in potassium bitartrate applying cation chromatography with direct conductivity detection. The USP41 monograph for “Potassium bitartrate” does not yet mention an assay for potassium. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). The assay of potassium is performed with two commercially available products according to USP definitions. All acceptance criteria are fulfilled.

Within the scope of the USP monograph modernization, potassium is determined in potassium sodium tartrate applying cation chromatography with direct conductivity detection. The USP41 monograph for “Potassium sodium tartrate” does not yet mention an assay for potassium. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). The assay of potassium is performed with two commercially available products according to USP definitions. All acceptance criteria are fulfilled.

Within the scope of the USP monograph modernization, potassium is determined in potassium bicarbonate effervescent tablets for oral suspension applying cation chromatography with direct conductivity detection. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). All acceptance criteria are fulfilled.

As an alternative to flame photometry, ion chromatography with non-suppressed conductivity detection has been approved by the USP as a validated method to quantify potassium and sodium content in potassium and sodium bicarbonates and citric acid effervescent tablets for oral solution. The present IC method has been validated according to USP General Chapter <621>.

As an alternative to flame photometry, ion chromatography with non-suppressed conductivity detection has been approved by the USP as a validated method to quantify potassium content in potassium bicarbonate and potassium chloride effervescent tablets for oral solution. The Metrosep C 6 - 150/4.0 column (L76) provides the required separation of potassium and magnesium. The present IC method has been validated according to USP General Chapter <621>.

Within the scope of the USP monograph modernization, sodium is determined in potassium sodium tartrate applying cation chromatography with direct conductivity detection. The USP41 monograph for «Potassium sodium tartrate» does not yet mention an assay for sodium. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). The assay of potassium is performed with two commercially available products according to USP definitions. All acceptance criteria are fulfilled. See AN-C-182 for the respective determination of potassium. Apllying this method allows to determine sodium and potassium simultaneously according to USP.

Calcium carbonate has a wide applicability in the pharmaceutical industry as an excipient and also as an active ingredient, and in the food industry as a major dietary supplement. The U.S. Pharmacopoeia (USP) monographs for calcium and magnesium carbonates tablets as well as calcium carbonate and magnesia chewable tablets currently describe manual titration as the assay procedure for calcium and magnesium. The USP has embarked on a global initiative to modernize many of the existing monographs across all compendia. In response to this initiative, two alternative analytical methods were developed to determine the analytes calcium and magnesium. This Application Note presents ion chromatography (IC) procedures using conductivity detection that provide better accuracy and specificity and are suitable for the intended purpose. These validated IC methods (according to USP General Chapter <1225>) offer a significant improvement to the existing assays because they can simultaneously determine both analytes calcium and magnesium, saving both time and effort.

The assay of calcium acetate, often used as a phosphate binder for dialysis patients, can be performed with ion chromatography (IC) as per USP <621> and <1225>.

Atorvastatin is a medication that is used for reducing cholesterol levels. A sensitive and reliable method for TBA detection is required, given that trace amounts of tetrabutylammonium (TBA) are to be found in the presence of atorvastatin and its derivatives. One such method is ion chromatographic separation on the Metrosep C Supp 1 - 250/4.0 with subsequent conductivity detection and sequential suppression.

The determination of the potassium content in foodstuffs plays a major role in the food and dietary supplement industry, as potassium is an essential mineral nutrient for humans. It is an important intracellular cation and also plays a important role in processes within cells, where it is involved in the regulation of numerous body functions like blood pressure, cell growth and muscle control.As a dietary supplement, potassium is present in e.g., electrolyte powder, electrolyte drinks and food supplements. To quantify the potassium content in such products, e.g. flame photometry can be used. In this work, an alternative, ion measurement by standard addition, is described, which is fast, inexpensive and simple to use.

This Application Note describes the determination of the water content in tablets using automated volumetric titration including sample preparation (MATi 11).

Alendronate, also referred to as alendronic acid, is a biphosphonate used to treat osteoporosis. It is the main ingredient in the tablets and is determined in accordance with the Chinese Pharmacopoeia (2015). Separation takes place in the Metrosep A Supp 4 - 250/4.0 column; direct conductivity detection is used for quantification.

Two of the leading pain remedies, aspirin and acetaminophen, are compared with generic samples for content uniformity testing using near-infrared spectroscopy (NIRS). The method of standard addition is used for quantification. To reduce most of the effects that stem from particle size and packing differences, second derivative spectra are used.

This Application Note shows the potential of NIRS as a rapid (< 30 s) and nondestructive screening tool for solid dosage forms (e.g. tablets). NIRS requires neither sample preparation nor solvent use. Interferences that derive from scattering are minimized by converting to second derivative spectra.

Well-mixed active substances for medications are indispensable in the pharmaceutical industry. This applies not only to the pharmaceutical active ingredient but also for lubricants, binding agents, explosives, oxidants and dyes. Analysis of these active ingredients is expensive; they are also only rarely analyzed as a rule. The progress of the mixing procedures can be followed conveniently with NIR spectroscopy, on the one hand using visual comparisons and on the other by means of spectral algorithms. The progress of mixing processes can be predicted in real time with the help of the spectrum when the latter is used.

This Application Note describes the utilization possibilities of a new sensor design that permits, in combination with an NIRS XDS Process Analyzer, the determination of solvent residues in a High-Shear Granulator during the drying phase. This system configuration reduces the scattering of the density distribution of the powder samples so that it is possible, directly in the process, to model the water and solvent content precisely.

This Application Note shows that NIR "predictive models" are optimally suitable for the non-destructive measurement of the release profiles of active ingredients from tablets. This is in accordance with the Process Analytical Technology (PAT) initiative of the FDA. The results demonstrate how NIRS considerably reduces the work involved for release studies in the laboratory.

Sulfathiazoles are sulfonamides with antibiotic effect that occur in various polymorphous forms and that are often used in veterinary medicine. This Application Note shows the differentiation between commercial and sulfathiazole form I using near-infrared spectroscopy (NIRS) with the help of the overtone frequencies of N-H stretching vibration. Form I is the least stable polymorphous form. Crystallization and polymorphism must be monitored as part of quality controls. In this, NIRS is considerably more rapid and more reliable than conventional laboratory methods.

This Application Note shows that visible near-infrared spectroscopy (Vis-NIRS) can be used for the quantification of Baicalin content in herbal supplements. Vis-NIRS is a good alternative to the conventional lab method (HPLC) and can save both cost and time.

This Application Note presents Vis-NIR spectroscopy as a viable alternative to determine API content in cefixime tablets without sample preparation.

The quantification of residual moisture in lyophilized pharmaceutical peptides is an important measure for quality control in the pharmaceutical industry. For development purposes, such measurements are necessary and routinely performed during stability studies and to optimize the freeze-drying process (lyophilization). Currently, Karl Fischer titration is widely used for moisture determination in routine analysis. However, this method is time consuming and destroys the sample during analysis. This Application Note shows that near-infrared spectroscopy (NIRS) is a fast, reagentless, non-destructive method to determine moisture content in lyophilized pharmaceutical products.

This Application Note shows how easy it is to determine water content in the pharmaceutical excipient lactose with reagent-free near-infrared spectroscopy.

Determination of citric acid and ascorbic acid in vitamin tablets using ion-exclusion chromatography with direct conductivity detection.

This Process Application Note provides a detailed account of the inline assessment of moisture during a pilot scale granulation process using a 2060 The NIR Analyzer.

In the pharmaceutical industry, the fluid bed granulator/dryer is an integral point in the manufacture of powdered materials. Residual moisture must be kept within certain specifications to avoid fracturing of particles or caking (stickiness) of the bulk material. Current methods are slow and cumbersome, which can lead to damaged or degraded product. The ability to monitor the residual moisture content inline after drying is possible with near-infrared spectroscopy (NIRS). The 2060 The NIR Analyzer offers fast, reagent-free, nondestructive analysis of residual moisture of powders with a fluid bed probe specifically designed for these applications.

Some samples, such as cosmetics and food, cannot be measured directly with the Rancimat as no evaluable induction time is obtained. There are many reasons for this, for example a high water content, a too low fat content or various matrix effects. However, using polyethylene glycol (PEG) as carrier material, many of these samples can be directly and reproducibly measured without sample preparation. This is due to the antioxidants that are naturally present in the sample matrix, and which stabilize the induction time of the PEG. The induction time can therefore be directly related to the oxidation stability of the sample.Furthermore, with a standard addition it is possible to measure the content of antioxidants (AOC) such as vitamin E, vitamin C or an equivalent of it. The decrease of the antioxidants over time (for example, during storage of the sample) can thus be measured and evaluated. In addition, this method eliminates a costly sample preparation. A reproducible and accurate determination of the oxidation stability using the 892 Professional Rancimat can be realized.

Producers of generic brands offer cosmetics, medicines and other goods in competition with name brands, often at a lower price point. This lower cost may reflect a lack of research, development, and advertising costs, but should never imply lower quality, especially in the case of over-the-counter drugs. As an example, Equate (a Walmart brand) effervescent cold tablets promise customers the same active ingredients in the same proportions and with identical effectiveness as Alka-Seltzer, at a much lower price. This Application Note demonstrates that Raman spectroscopy can successfully verify that these competing cold tablets are not identical. The process of ingredient verification involves a p- test, which measures the acceptable variability of a sample spectrum, as compared to a representative training set.

Raman spectrometers use tightly focused beams to produce high resolution spectra, but fail at analyzing heterogeneous substances because they cannot spatially target all components. ORSTM (Orbital Raster Scan) increases the interrogation area on a sample while maintaining high spectral resolution. Effervescent cold medicines, for example, contain many active ingredients in each heterogeneous tablet. Traditional identification and verification techniques require the collection of several spectra at different points on the tablet. Mira spectrometers equipped with ORS capture a large interrogation area in a very short time, analyzing all of the ingredients in a single scan.

Handheld Raman spectrometers are valued for their ability to provide onsite material identification in seconds. In the case of combination pharmaceuticals, a single tablet contains more than one active ingredient in different proportions. MIRA DS is uniquely capable of identifying multiple compounds in such tablets by using Raman to identify the major component and SERS (surface-enhanced Raman spectroscopy) for the minor component. This application describes quick, dual analysis of a prescription medication containing acetaminophen and hydrocodone. The application is easily extrapolated to the study of street drugs.

Yaba, produced in Southeast Asia, is a popular drug of abuse and is actively targeted by police squads. Two strong and highly addictive stimulants make up Yaba: caffeine, which comprises up to 60% of each tablet, and methamphetamine at approximately 20%. Identifying these two active ingredients in different proportions in a colorful tablet with other excipients could be an analytical nightmare. With handheld Raman, bulk material identification is achieved in seconds onsite with simple point-and-shoot analysis. SERS (surface-enhanced Raman spectroscopy) analysis is used to detect the minor component in mixtures without interference from fillers, dyes, and coatings. MIRA DS is uniquely capable of both analyses—Raman testing positively identifies caffeine in Yaba, while methamphetamine can be detected with SERS sampling. This application describes quick, dual analysis of Yaba tablets with MIRA DS.

This application note presents the Orbital Raster Scan (ORS) technology from Metrohm Raman to overcome low resolution, poor sensitivity, and sample degradation while still interrogating a large sample area.

Determination of fluoride, sulfate, iodide, and molybdate in mineral tablets using anion chromatography with conductivity detection after chemical suppression.

Determination of chloride in bethanechol tablets using anion chromatography with conductivity detection after chemical suppression.

Determination of fluorophosphate in effervescent tablets using anion chromatography with conductivity detection afterchemical suppression applying a step gradient to elute strongly retained components.

Determination of acetate and methanesulfonate (MSA) in olsalazine using anion chromatography with conductivity detection after chemical suppression.

Topiramate is an antiepilepsy drug. According to USP Topiramate tablets have to be tested for impurities. The determination of sulfate and sulfamate is mentioned under 'Specific Tests'. The isocratic method applies a column eluent combination primarily used for non-suppressed IC. But as sulfamate shows a negative peak under theses conditions the use of suppression is advantageous.

Potassium chloride and potassium bicarbonate effervescent tablets are used to prevent potassium deficiency. Pharmaceutical manufacturers and labs adhere to strict quality regulations using USP-NF monographs. Ion chromatography with suppressed conductivity detection, utilizing the Metrosep A Supp 16 - 100/4.0 (L91) column, is approved by the USP to quantify chloride content in these tablets, following validation per USP General Chapter <621>.

Sodium fluoride tablets for pharmaceutical use need to comply with U.S. Pharmacopeia (USP) requirements. Ion chromatography (IC) with suppressed conductivity detection has been approved by the USP as a validated method to quantify fluoride content in sodium fluoride tablets. In the course of the USP monograph modernization, using automated IC makes this type of analysis even easier.

As an alternative to titration, ion chromatography (IC) with suppressed conductivity detection has been approved by USP as validated method to quantify chloride content in NaCl tablets for solution or oral use.

Nitrosamine presence in medicines, even at trace level poses high safety risks to patients (carcinogenic). Nitrosamine formation can be avoided by controlling and monitoring the nitrite concentration in pharmaceutical products and substances. This Application Note describes the analysis of nitrite in duloxetine hydrochloride with ion chromatography (IC).

Nitrosamine formation can be avoided by controlling the nitrite concentration in pharmaceutical products and processes. To monitor nitrosamine formation, sensitive analytical methods such as ion chromatography for the determination of nitrite in pharmaceutical products and substances are essential.

This Application Note demonstrates square wave voltammetry for sensitive, reproducible quantification of paracetamol using a screen-printed electrode and INTELLO.

Determination of the antihistamine astemizole in raw products by nonaqueous potentiometric titration with perchloric acid using separate electrodes.

This Application Note details the photometric determination of chondroitin sulfate with 1-hexadecylpyridinium chloride as titrant and with the Optrode (660 nm). The method is in compliance with the Ph. Eur. and the USP.

This Application Note describes the photometric determination of bismuth nitrate using the Optrode (520 nm). The sample is titrated with EDTA solution past the endpoint; xylene-orange is used as the indicator. The method for bismuth nitrate fulfills the directives defined in the Ph. Eur. and the USP.

This Application Note looks at the photometric determination of manganese sulfate using the Optrode (610 nm). Manganese is titrated with EDTA; Eriochrome Black T is used as indicator. The method complies with Ph. Eur. and the USP.

This Application Note describes the photometric determination of zinc sulfate using the Optrode at a wavelength of 610 nm. Complexometric titration of zinc requires EDTA as titrant and Eriochrome Black T as indicator. The method fully complies with Ph. Eur. and USP.

In accordance with the European Pharmacopoeia, sodium sulfate is determined with the PB ISE.

This Application Note describes the nonaqueous acid-base titration of ketoconazole in accordance with the European Pharmacopoeia. The Solvotrode easyClean was used as the electrode.

The composition of salts with laxative and expectorant effects must be determined precisely in medications. The sulfate content is determined using automatic potentiometric titration with EGTA as titrant in accordance with Ph. Eur. 8.0.

Metformin is one the most commonly used drugs for diabetes type 2 belonging to the group of biguanides. This Application Note describes the determination of metformin hydrochloride assay according to USP using acetic anhydride as solvent.

Penicillin and its related antibiotics are used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, etc. It may also be used to prevent group B streptococcal infection in newborns. The β-lactam ring of penicillin binds to the enzyme DD- transpeptidase, which prevents the formation of cross links during cell wall formation of new bacterial cell, i.e., the division of bacterial cells. USP<425> describes a back-titration method to determine the assay of pharmacopeial penicillin antibiotic drugs and their dosage forms by iodometric titration. The method is illustrated by determining the aminopenicillin content in an ampicillin capsule.

Sulfonamides are drugs used to treat allergies and cough. They also have some antifungal and antimalarial activities. USP<451> describes nitrite titration method for the determination of numerous pharmacopeial sulfonamide drugs and their dosage forms as well as of other pharmacopeial drugs with, for example, hydrazide (e.g., in isoniazid) and amine ester groups (e.g., in procaine) or amide derivatives of amino acids.Here, for illustrating the analysis of the latter, the assay of the diagnostic agent aminohippuric acid is described.

Kjeldahl method is used to determine the nitrogen content in organic and inorganic samples. Kjeldahl consists of three steps: digestion, distillation, and titration. During the catalytic digestion step, organic nitrogen is converted into ammonium. Sodium hydroxide is added just before the distillation step for converting ammonium into ammonia. Through steam distillation the latter is transferred into the receiver vessel containing an absorbing agent (e.g., boric acid). Finally, the separated ammonia is titrated against sulfuric acid. Protein content in samples can also be determined from the nitrogen content obtained by Kjeldahl setup. USP describes the titration method to determine nitrogen content in organic products using Kjeldahl nitrogen setup. This Application Note illustrates nitrogen determination in heparin sodium.

Vitamin C, also known as ascorbic acid or L-ascorbic acid, is an essential nutrient involved in the repair of tissues and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and immune performance, and is also an important antioxidant. This nutrient is found in many foods and is often used as a dietary supplement.USP general chapter <580> describes a titration technique to determine the assay of Vitamin C as ascorbic acid, sodium ascorbate, and calcium ascorbate dehydrate, or their mixture in finished dosage forms as capsules, tablets, and oral suspensions. This Application Note demonstrates the Vitamin C determination in water-soluble vitamin tablets. The methodology can also be applied for oil-soluble vitamin or mineral tablets, as well as oil- and water-soluble vitamin or mineral capsules.

This Application Note presents a potentiometric titration method for a potassium bicarbonate and potassium carbonate assay meeting all USP General Chapter <1225> requirements.

Direct titration is a simple and precise way to accurately measure the caffeine content in different nonaqueous products. The OMNIS Titrator equipped with a dSolvotrode reliably determines caffeine through flexible analyses combined with high-end software.

The iodometric back titration is a precise method used to accurately measure the caffeine content in various aqueous samples. Reliable determinations are made easy using the OMNIS Titrator equipped with a dPt Titrode.

The amine value is an important parameter and quality indicator to determine in chemical processes and pharmaceuticals. This Application Note presents the nonaqueous perchloric acid titration of triethanolamine.

Determination of N-acetylcysteine and phenylalanine in tablets against sinusitis by anion chromatography with UV/VIS detection according to USP.

Determination of salicylic acid and acetylsalicylic acid according to USP 28-NF 23 (second supplement) using RP chromatography with UV detection.

Determination of theophylline and theobromine according to USP 28-NF 23 (second supplement) using RP chromatography with UV detection.

Determination of valerophenone and ibuprofen according to USP 28-NF 23 (second supplement) using RP chromatography with UV detection.

Determination of ranitidine hydrochloride according to USP 28-NF 23 (second supplement) using RP chromatography with UV detection.

Determination of cefadroxil in accordance with USP 28-NF 23 (Supplement 2) using RP chromatography with UV detection. Keyword: Antibiotics

Paracetamol is an effective antipyretic and analgesic. Its determination in tablets using reverse phase chromatography and UV detection is quick and easy with the sample preparation described in this Note. The 815 Robotic Soli Prep for LC does everything automatically: from dissolving the tablets, homogenizing and filtering, to 250-nL-Loop injection.

Determination (after digestion) of zinc, cadmium, lead, copper, nickel, and cobalt in fabrication powder of vitamin tablets.

Determination of manganese, iron, and molybdenum (after digestion) in fabrication powder of vitamin tablets.

Determination of artemisinin and artesunate in a standard.

Determination of ascorbic acid (vitamin C) in vitamin capsules after sample digestion.

Riboflavin (vitamin B2) can be determined in vitamin preparations at the DME.

Nicotinamide (vitamin B3, vitamin PP) can be determined in vitamin preparations at the DME.

The NanoRam handheld Raman, with a TE-cooled spectrometer, and patented CleanLaze technology packaged in a small, touch-screen operating unit, delivers high quality raw material testing capabilities for pharmaceutical manufacturers.

The NanoRam is a state-of-the-art, handheld Raman spectrometer for the rapid identification of chemicals used in the pharmaceutical manufacturing process. It has been specifically designed for these applications and is fully compliant with all the major global regulatory, safety, and commercial testing agencies applicable to the pharmaceutical industry.

Raman spectroscopy is a valuable tool to provide rapid, specific analysis for identification of raw materials, thus reducing the risk of using substandard or incorrect materials in manufacturing. The utility of handheld Raman increases productivity, and the ability to do full testing without creating bottlenecks in the production process. The integration of the Raman data into a company’s data management system provides a secure means of handling data and results, with reduced risk of transcription errors, and data loss.

Content uniformity of solid dosage forms can be done nondestructively at the process line using the QTRam portable transmission Raman system.

The pharmaceutical industry is very likely more comprehensively regulated that any other branch of industry. It therefore requires analytic methods that meet the requirements of regulations while at the same time being practical. This applies in particular for large sample quantities, such as are encountered with incoming goods inspections, for example. It is here that particularly rapid and simple analysis methods are called for which make routine analyses simpler and more efficient. This White Paper describes some of the most important regulations in the pharmaceutical analysis and shows how Vis-NIR spectroscopy can solve analytic problems in the pharmaceutical industry in accordance with regulations.

Ion chromatography is a flexible technique with a large selection of intended uses in the pharmaceutical industry. – A few development trends and the latest advances are displayed here.

Chemometrics is a powerful tool widely used for method development in the pharmaceutical industry. This whitepaper describes the lifecycle of multivariate models and summarizes the workflow of the development of chemometrical models according to the new USP chapter <1039>.

High-Performance Liquid Chromatography (HPLC) and Ion Chromatography (IC) are commonly used in the pharma, food, and environmental sectors to analyze samples for specific components and to verify compliance with norms and standards. However, users of HPLC may run into the limitations of this technique, e.g., when analyzing standard anions or certain pharmaceutical impurities. This white paper outlines how such challenges can be overcome with IC.

Underestimation of quality control (QC) processes is one of the major factors leading to internal and external product failure, which have been reported to cause a loss of turnover between 10–30%. As a result, many different norms are put in place to support manufacturers with their QC process. However, time to result and the associated costs for chemicals can be quite excessive, leading many companies to implement near-infrared spectroscopy (NIRS) in their QC process. This paper illustrates the potential of NIRS and displays cost saving potentials up to 90%.

This white paper summarizes the steps involved in converting an existing manual titration procedure to semi-automated or automated titration procedures. It discusses topics such as selecting the right electrode and titration mode. For a better understanding, the discussion topics are illustrated with three examples.

The objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended purpose. Recommendations for the validation of analytical methods can be found in ICH Guidance Q2(R1) Validation of Analytical Procedures: Text and Methodology and in USP General Chapter <1225> Validation of Compendial Procedures. The goal of this white paper is to provide some recommendations for the validation of titration methods.