News from LabRulezLCMS Library - Week 35, 2025

Our Library never stops expanding. What are the most recent contributions to LabRulezLCMS Library in the week of 25th August 2025? Check out new documents from the field of liquid phase, especially HPLC and LC/MS techniques!

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This week we bring you poster by Agilent Technologies / ASMS, brochure by Shimadzu, other document by Thermo Fisher Scientific and application note by Waters Corporation!

1. Agilent Technologies / ASMS: Highly Sensitive Quantitation of N-Nitroso Timolol Impurity in Timolol API using the Agilent 6495D LC/TQ

• Poster
• Full PDF for download

Nitrosamines are of concern as most of them have been reported to be potent mutagens in rodents and are potential carcinogens. Therefore, it is important to control these impurities at or below the stipulated specification limits. API-derived complex nitrosamines are known as nitrosamine drug substance-related impurities (NDSRIs). Multiple recalls of pharmaceutical drug products due to the presence of NDSRIs have drawn the attention of regulators and manufacturers. By considering the complexity of the global pharmaceutical supply chain, manufacturers must be more diligent to protect consumers by screening their APIs and drug products for the presence of NDSRIs. NDSRIs can be formed from both secondary and tertiary amines. Secondary amines can easily undergo nitrosation in the presence of trace amounts of acid. Timolol is beta-blocker class of drug used for hypertension. N-nitroso timolol is an API specific nitrosamine impurity. For most NDSRIs, analytical methods are not yet available, so manufacturers will need to develop, qualify, and validate a method that is suitable for the sample matrix and specific for the nitrosamines in question.

The analytical method developed must be sensitive enough to quantify the nitrosamines of interest down to a level that corresponds to 10% of specification limit.

In this poster we highlight a highly specific, sensitive, and reproducible method that was developed for the quantitation of N-nitroso Timolol impurity in Timolol drug substance using the 6495D triple quadrupole LC/MS (LC/TQ) coupled to the 1290 Infinity II LC.

Experimental

LC configurations and parameters:

• Instrument: Agilent 6495D LC/TQ coupled to 1290 Infinity II LC
• Analytical Column: Agilent Infinity Lab Poroshell PhenylHexyl, 150 × 3.0 mm, 2.7 µm, p/n, 693975-312

Conclusions

A highly sensitive and robust multiple reaction monitoring (MRM) method was developed utilizing the Agilent 6495D LC/TQ to quantify N-nitroso timolol impurity in timolol API.  

• The chromatographic method provided desirable separation between the impurity and the API to avoid interference. 
• The developed method demonstrated excellent linearity over the range of 5 to 1500 pg/mL (0.5 to 150 ppb with 100 mg/mL API load) with an R2 value greater than 0.9990 
• The LOD and LOQ values achieved were 2 and 5 pg/mL respectively for targeted NDSRI 
• The method provided recovery between 90 and 110%, which is within the acceptance criteria

2. Shimadzu: Liquid Chromatograph Mass Spectrometer LCMS-8065XE 

• Brochure
• Full PDF for download

Shimadzu LCMS-8065XE: Next-Generation Triple-Quadrupole Performance

Shimadzu introduces the LCMS-8065XE, a triple-quadrupole liquid chromatograph mass spectrometer designed to set new standards in sensitivity, speed, and robustness. Built on Shimadzu’s philosophy of “Contributing to Society Through Science and Technology,” the system integrates advanced hardware with Analytical Intelligence software, ensuring both expert-level optimization and user-friendly operation. This balance of evolved, efficient, and exact capabilities makes the LCMS-8065XE a powerful solution for modern laboratories.

Breakthrough Ionization and Detection Technologies

At the heart of the system are innovations such as the StreamFocus ESI probe and IonFocus technology, which enhance ion intake, reduce gas consumption, and eliminate contamination without compromising sensitivity. Combined with the refined UFsweeper IV collision cell, the instrument achieves exceptional signal transmission and robust long-term stability. Demonstrated by ultra-trace PFAS detection at parts-per-trillion levels, the LCMS-8065XE ensures reliable results even under continuous high-throughput conditions.

Ultra-Fast Mass Spectrometry with UF Technologies

Shimadzu’s proprietary UF technologies—including UF-Qarray II, UF-Lens II, and UF-MRM—deliver unmatched speed and sensitivity. Capable of 5 msec polarity switching, up to 555 MRM channels per second, and scanning at 30,000 u/sec, the system supports complex multi-component analyses with precision. Intelligent maintenance features, such as quick desolvation line replacement without breaking vacuum, further minimize downtime and maximize laboratory productivity.

Smart Software, Sustainability, and Seamless Integration

The LCMS-8065XE is complemented by Peakintelligence AI algorithms, LabSolutions Connect MRM, and LabSolutions Insight, enabling automated tuning, optimized methods, and reliable peak integration with reduced manual review time. Sustainability is also central: ecology mode reduces power consumption by up to 31%, while integration with Shimadzu’s Nexera UHPLC system improves throughput and reduces resource use. Features like FlowPilot smart flow control and automatic bubble detection ensure uninterrupted performance, extending system and column lifetimes while cutting operational costs.

3. Thermo Fisher Scientific: Accucore columns Resolve all your impurities without feeling the pressure

• Other document
• Full PDF for download

Thermo Scientific™ Accucore™ columns bring UHPLC-level performance to both HPLC and UHPLC systems, even when pressure capabilities are limited. With 14 distinct chemistries, they provide an extensive toolbox for successful method development and robust method transfer. Built on decades of innovation in stationary phase design, Accucore columns ensure reliable performance across diverse analytical challenges.

Comprehensive Chemistry Portfolio for Any Separation Need

The Accucore family includes multiple column chemistries tailored to different selectivity requirements. Hydrophobic options like C18, C8, and C4 deliver classic reversed-phase separations, while polar-modified C18 (Polar Premium, aQ) enhances retention of acidic and basic compounds. Phenyl-based phases such as Biphenyl, Phenyl-Hexyl, and PFP provide orthogonal selectivity for aromatic and polar analytes, and specialty hydrophobic columns (RP-MS, C30) expand capabilities for structural isomer separation. For highly polar compounds, HILIC and Amide-HILIC chemistries enable reliable retention and resolution.

Optimized for Speed, Sensitivity, and Versatility

Engineered with advanced particle design, Accucore columns offer rapid separations with high resolution and reproducibility. Their versatility makes them suitable for a wide range of applications, from pharmaceutical impurity profiling to food and environmental analysis. By offering both routine and specialty phases, the columns allow analysts to fine-tune selectivity and maximize productivity without compromising robustness.

Trusted Innovation and Seamless Integration

As part of Thermo Fisher Scientific’s portfolio, Accucore columns are backed by extensive expertise in HPLC method development and transfer. Their design supports high-throughput workflows, smooth integration into existing systems, and consistent results across laboratories. Whether the need is for routine testing or complex separations, Accucore columns deliver dependable performance with the flexibility to resolve impurities efficiently and confidently.

4. Waters Corporation: Temperature Control Using Waters LC Purification Systems with Timberline's Column and Mobile Phase Heaters: Optimizing Preparative Performance 

• Application note
• Full PDF for download

Benefits 

• Minimizing method redevelopment at the prep scale improves process efficiency and reproducibility, ensuring predictable and reliable outcomes for isolating small and large molecules, such as oligonucleotides and peptides. 
• Elevated temperature reduces system backpressure and enables one to consider using of sub-5 µm Waters™ preparative Optimum Bed Density (OBD™) columns to increase productivity through faster separations, increased loading capacity, lower solvent consumption, shorter fraction dry-down times, and reduced waste disposal costs. 
• Enabling the substitution of acetonitrile with methanol provides a more environmentally sustainable and economically efficient purification process.

Although temperature control is widely implemented in analytical HPLC to improve separations and ensure consistent and reliable outcomes, temperature is seldom controlled or used as a parameter for manipulating chromatography at the preparative scale for two reasons. First, high flow rate separations occur at the temperature of the incoming solvent and efficient heating of the mobile phase entering the column is challenging at these high flow rates. Second, large diameter columns cannot be effectively heated from the outside simply by using insulation, heated blankets or ovens. Ideally, analytical separations developed with temperature control should be scaled to prep at the same temperature to eliminate variability in the chromatography which can make the target identification and isolation ambiguous or lead to product loss. 

When used with the Waters AutoPurification System, Timberline’s column and mobile phase heaters provide precise and consistent temperature control for preparative separations, allowing easier scale-up from UPLC/UHPLC to preparative methods. This integrated approach minimizes the need for method redevelopment, improves reproducibility, enhances hydrophobic compound solubility and boosts operational efficiency, which is particularly valuable in small molecule isolations and biological applications such as oligonucleotide and peptide purification. Temperature control also enhances flexibility in purification workflows, supporting green chemistry initiatives by enabling the substitution of acetonitrile with methanol. Elevated temperature reduces system backpressure, allowing the usage of sub-5 µm particles in larger-dimension preparative columns (e.g., 10 mm ID), which may increase loading capacity, minimize run-times, reduce solvent consumption, shorten dry-down times and lower waste disposal costs. This technical brief illustrates that comparable purification results can be achieved using methanol with sub-5 µm 10 mm ID columns, an approach that is both environmentally sustainable and economically viable. It also illustrates the precision and stability of temperature control across various flow rates and mobile phase compositions, showcasing the reliability of this solution.

Conclusion 

Timberline’s TL-105 D column oven configured with the Waters AutoPurification System provides precise and consistent temperature control when scaling from analytical to preparative methods. This significantly reduces the need for method redevelopment at the prep scale, enhances chromatographic efficiency and reproducibility and delivers predictable and reliable outcomes for various applications including small and large molecules such as oligonucleotides and peptides isolations.

This combined solution supports the growing demand for green chemistry by enabling the substitution of acetonitrile with methanol. Enhanced temperature control also lowers system backpressure, allowing the use of smaller particle size, larger dimension Waters preparative OBD columns. This results in faster separations, increased loading capacity, reduced solvent consumption, shorter fraction dry-down times, and lower waste disposal costs. These benefits contribute to a more environmentally sustainable and economically efficient purification process.