Shimadzu Europa GmbH

Ultrapure water is essential for pharmaceutical production, requiring complex treatment process to maintain its purity. Strict regulations prescribe parameters such as conductivity, Total Organic Carbon (TOC) and microbial levels to ensure its purity. By implementing Process Analytical Technology (PAT) and using Shimadzu’s TOC-1000e, pharmaceutical manufacturers can ensure consistent water quality, minimize contamination risks and comply with regulations.

Shimadzu’s TOC-1000e, a state-of-the-art process analyzer, specializes in this field. It employs fast oxidation technology and a mercury-free excimer lamp to accurately measure TOC content and electrical conductivity. Its advanced features include an extended 12-month maintenance cycle, which reduces plant downtime and enhances productivity. By doubling the maintenance cycle duration from the industry-typical 6 months to 12 months, TOC-1000e minimizes water plant downtime, which translates into increased productivity and efficiency in production facilities. Additionally, the longer maintenance cycle decreases calibration and validation efforts.

TOC-1000e meets pharmacopoeial regulations and incorporates user management, audit trail functionalities and can be seamlessly integrated with electronic signature platforms to facilitate compliance with data integrity requirements such as 

With its precise analysis capabilities, the TOC-1000e empowers pharmaceutical manufacturers to uphold the highest standards of water quality, ensuring purity and integrity throughout the production process.

For more information on the TOC-1000e, click 

Shimadzu Europa GmbH
Albert-Hahn-Straße 6–10
47269 Duisburg


Articles

Take ultrapure water monitoring to new heights using Shimadzu’s TOC-1000e. Benefit from a 12-month maintenance interval, resulting in reduced plant downtime, cutting calibration and revalidation effort in half.

Shimadzu TOC-1000e

Shimadzu's Nexera Prep – Preparative and Purification LC

The new Nexera Prep - preparative and purification LC system is a cutting-edge tool for efficient preparative work. It improves productivity tremendously while providing better prep processes for drug discovery and purification of functional components. The Nexera Prep enables customer- and application-specific solutions supported by a wide choice of equipment, accessories and process automation. Depending on the units applied, Nexera Prep covers LC and LC-MS solutions serving users’ demands, such as multi-sample and multi-fraction analysis, effective separation at low cost, purity confirmation of collected fractions and automated desalting, concentration, purification and recovery. With ease-of-operation in a flexible set-up, the combination of new hardware and software features increases productivity dramatically through time- and labor-saving benefits, while at the same time reducing solvent and sample consumption.

Nexera Prep minimizes the time required for investigating preparative work conditions, enables seamless processes such as purity checks through re-injection of collected sample, offers a sample rescue protocol in case an error occurs after an injection and automates high-purity preparative purification. Nexera Prep also contributes to laboratory efficiency through space saving design and a small installation footprint, which is only about half the size of competing products in the same class.

The Nexera Prep preparative and purification LC improves productivity via efficient preparative work using application-specific LC (-MS) solutions. It provides better prep processes for discovery and purification of functional components.

 is designed to deliver high-resolution, accurate mass detection with incredibly fast data acquisition rates, allowing scientists to identify and quantify more compounds with greater confidence.

It utilizes the same engineering DNA as Shimadzu’s proven, rugged, high-performance triple quadrupole (LC-MS/MS) platform and integrates this with powerful TOF architecture to transform high mass accuracy workflows by achieving high-sensitivity, high-speed and high-resolution detection. The LCMS-9030 provides effortless performance through less need for calibration and easy switching between ionization units.

Ultra-fast (UF) acquisition rates and core ion beam technologies developed for the triple quadrupole platform have created new possibilities in quantitative mass spectrometry by delivering exceptional sensitivity, specific quantitation and enhanced target compound verification. The 

 Q-TOF builds on this proven platform by rethinking time-of-flight detection.

In the LCMS-9030, core ion beam technologies transition towards a unique approach in ion gating using UFaccumulation™to create a precise pulse of ions in the flight tube optimized for high sensitivity and high resolution using iRefTOF™reflectron technology. The iRefTOF™ generates an ideal reflectron field, delivering the highest resolution for the flight path with highly stable mass accuracy.

New solution for analyzing even the most complex samples

By bringing together UF technologies and innovative TOF thinking, the 

 represents a step-change in Q-TOF performance and capability by unlocking a new solution for analyzing even the most complex samples. It integrates the world’s fastest and most sensitive quadrupole technology with TOF architecture.

UFaccumulation and iRefTOF are registered trademarks of Shimadzu Corporation

Shimadzu’s LCMS-9030 is designed to deliver high-resolution, accurate mass detection with incredibly fast data acquisition rates, allowing scientists to identify and quantify more compounds with greater confidence. 

Effortless Performance: The LCMS-9030 Q-TOF

 is the first analyzer in the eTOC series of online TOC analyzers designed for pure water applications. The eTOC series’ main focus is on miniaturization, high sensitivity and a mercury-free oxidation technique. The pioneering TOC-1000e system has the world’s smallest and lightest cabinet and provides high-sensitivity detection, making it ideal for fields requiring high-purity water applications. This covers manufacturing, including pharmaceuticals, semiconductors, food & beverages, chemistry and precision equipment.

Total organic carbon (TOC) analyzers are used to rapidly quantify organic substances in water, allowing decisive process intervention. Among many fields of application, they are used mainly for water quality control and environmental investigations. Shimadzu’s world-leading TOC analyzers are well-suited to laboratory and on-line analysis of environmental and waste water. The eTOC series will be Shimadzu’s first on-line TOC analyzer designed especially for pure water measurements.

Minimum footprint, highly sensitive, environmental-friendly

 provides enhanced robustness in the ultra-low measurement range. With its small footprint of less than A4 size, it can be installed flexibly – either as table-top, wall-mounted or pole-mounted.

Conventional TOC analyzers for pure water utilize mercury UV lamps as the light source within the instrument. To provide a more environmental-friendly alternative, the eTOC series is the first analyzer in the world to use an excimer (short for ‘excited dimer’) lamp rather than a mercury lamp.

The “Active-Path” flow line design maximizes lamp power by integrating the sample flow channel and the light source. This minimizes sample residue in the flow channel and eliminates interfering air layers, so high sensitivity is maintained over long-term use. This new design also contributes to making the eTOC series instruments small and light.

The TOC-1000e combines high-sensitivity and easy-to-use features benefiting effortless data management, efficiency and handling. To mention just a few:

State-of-the-art oxidation technology in the smallest casing

 provides high sensitivity with a detection limit of 0.1 μg/L. It is housed in the world’s smallest and lightest cabinet and equipped with the industry’s largest color touch panel, providing exceptional visibility, simplifying operation and allowing effortless management of compliance relevant data. In addition, the novel fluid system minimizes sample residue in the flow channel, ensuring that high sensitivity is maintained.

Easy-to-use and to maintain design improves efficiency


The eTOC series has a simple design, and parts typically do not need to be replaced for one year; this increases efficiency by reducing maintenance and re-validation effort. Consumable parts (excimer lamp and pump head) can be removed and installed without tools. Using an optional sampler, the analyzer can be calibrated or validated (confirmation of manufacturing process validity) at the operating site. Certified standard solutions particularly for this series are available; they save customers the time and expense of purchasing and preparing items from a reagent manufacturer, and reduce mistakes caused by human error. In addition to analog interface and digital I/O, measurement data can be output to a printer or USB flash drive, or browsed and acquired via a built-in web server.


TOCs’ highly sensitive UV oxidation-conductivity method for ultra-pure water monitoring is compliant with regulatory requirements such as the United States (USP) and the European Pharmacopeia (EP). Inbuilt security functions including user authentication and audit trail, support compliance with regulations such as FDA 21 CFR Part 11. The LabSolutions software platform provides integrated management of the measurement data together with data and electronic signature functions (ER/ES) from laboratory TOC analyzers and other analytical instruments.

Shimadzu’s TOC-1000e is the first analyzer in the eTOC series of online TOC analyzers designed for pure water applications. The eTOC series’ main focus is on miniaturization, high sensitivity and a mercury-free oxidation technique.

TOC-1000e: On-line TOC analyzer designed for pure water  applications

	Environmental and pharmaceutical application, forensics, material and food production analyses – Shimadzu’s 

 serves GC and GCMS applications particularly in testing and inspection organizations. The HS-20 covers accurate analysis of an even wider range of vola-tile compounds with boiling points ranging from low to high. The HS-20 heats liquid or solid sam-ples sealed in a container to a specific temperature, and injects the volatile compounds diffusing into the gaseous phase into a 

Shimadzu’s HS-20 headspace sampler serves GC and GCMS applications particularly in testing and inspection organizations. 

HS-20 headspace sampler for GC and GCMS

 automated pretreatment module is for pretreating of culture media samples by adding reagents such as a deproteinizing agent or internal standard substance, filtering of precipitated proteins, and diluting of samples.

 module with a Shimadzu ultra-fast liquid chromatograph mass spectrometer (LC-MS/MS). By automating all the process steps from pretreatment to measurement, the C2MAP system shortens the culture media analysis time for up to 95 components in culture supernatants to one sixth of the previous level. In addition, this system can be operated by less experienced operators.

	After simply loading culture supernatant samples, reagents and pairs of filter and recovery vials, the C2MAP-2000 module is able to execute all steps from pretreatment to LC-MS/MS measurement without any human intervention. This seamless execution not only makes it easy to process samples unattended overnight or on non-working days, but also enables samples to be controlled using the same ID for all process steps. This minimizes the risk of selecting the wrong sample while ensuring traceability. 

-TRENDS time-course viewer software loads the measurement data obtained and graphs temporal changes in each component concentration as trend graphs.

Growing importance of LC-MS/MS analysis to optimize cell culture conditions

	In recent years in antibody pharmaceutical fields, it has become increasingly important to record the consumption of components and accumulation of waste matter (secreted metabolites) in culture media, so that cell cultivation parameters can be optimized for manufacturing drug substances. In addition, in regenerative medicine fields that involve iPS, ES or other cells, there is a need for technology that can evaluate cell quality in real time without damaging the cells. There is also a need to reduce the replacement frequency of expensive culture media. Since monitoring the changes in culture supernatant components over time provides information that is useful in these fields, the role of 

/MS analysis has increased in the optimization of cell culture conditions.

	However, due to the lack of products available for seamlessly performing of all processes from sample preparation to measurement, there was a need for a system that could be used easily, even by less experienced operators. Shimadzu therefore developed the 

 automated pretreatment module and the C2MAP system for steps involved in determining the status of cultures and researching cultivation process steps at major pharmaceutical companies, biotech ventures, pharmaceutical CMOs (contract manufacturing organizations) and various research institutions. In the future, Shimadzu intends to offer solutions based on 

/MS measurement technology for controlling and optimizing of cell cultivation process steps.

	C2MAP and C2MAP system are registered trademarks or trademarks of Shimadzu Corporation.

Shimadzu’s C2MAP-2000 automated pretreatment module is for pretreating of culture media samples by adding reagents such as a deproteinizing agent or internal standard substance, filtering of precipitated proteins, and diluting of samples.