MS-compatible methods

The outcome of planning should include the generation of a method definition requirement document (MDRD) in which all stake holders agree, prior to method development, on the critical attributes of the method. Considerations such as what impurities/degradation products should be monitored, requisite reporting thresholds, the need for an MS-compatible method, if identical methods for DP and DS are required, etc., should be clearly decided and agreed upon by all stakeholders. 

MS-compatible methods to facilitate identification of unknowns often encountered during process development and early stability studies. 

Michishita T, Franco P, Zhang T. New approaches of LC-MS compatible method development on al-acid glycoprotein-based stationary phase for resolution of enantiomers by HPLC. J. Sep. Sci. 2010 33 3627-3637. 

MS compatibility is not a must, but preferred. For achiral purity methods an alternative MS compatible, supportive method is available to support identification... 

IPC-MS combined methods must be optimized with respect to separation and compatibility with online detection involving the constraints detailed in Table 12.2 regarding the composition and volatility of the mobile phase. The major concern of chromatographers who deal with this combined technique is the reduced signal caused by source pollution of non-volatile IPRs. Moreover, the efficiency of droplet development, which in turn affects the number of charged ions that ultimately reach... 

Identifying an unknown by using a standard, as described in the above paragraph, is a quick and easy process. However, what happens when the relative retention time of an unknown does not match that of a standard The next step is to obtain molecular mass and fragmentation data via HPLC/ MS. It is essential to determine the molecular mass of the unknown. Not only does the molecular mass help in the identification of the unknown, but it also enables one to track the correct peak by HPLC if isolation becomes necessary. In order to run LC/MS, a mass spectrometry compatible HPLC method must be available. The mobile phase should contain volatile buffers that are HPLC/MS-compatible. If such a method is not available, then one must be developed, which adds time to the identification time frame. 

The purity was lower than desirable for NMR analysis, so further purification was undertaken to facilitate structure elucidation by NMR. The existing analytical methodology contained perchloric acid that was not suitable for preparative HPLC isolation and LC/MS analysis because of safety concerns with concentration of perchloric acid and high probability of damage to the mass spectrometer over time. A mass spectrometry compatible method using a 0.1% acetic acid buffer was selected as a starting point. Minor method development produced a suitable method to separate the reaction components the drug substance, the sulfoxide, and the N-oxide. 

Trends toward MS-compatible, gradient methods for impurity testing... 

Although most pharmaceutical methods use UV detection, the importance of adopting MS-compatible mobile phases cannot be overemphasized. MS is... 

Emission spectroscopy (e.g., ICP-AES, ICP-CATS, or ICP-MS) techniques are moving to the forefront of copper determination after the instruments became available at affordable prices during the 1990s. Today, ICP-MS has reached detection limits of 5 to 50 ng Cu which renders ICP-MS compatible with ASV and CSV methods for copper determination (Lu et al. 1993). The advantages of ICP-MS include simultaneous determination of the sample multi-element profile and the assessment of isotopic species. All the measures available should be taken to prevent external contamination of the samples blanks and certified reference materials (CRMs) are the condi-... 

Sample Preparation Normally, biological samples are not directly compatible with LC-MS/MS analysis, and they need to be processed before delivery to the LC-MS system. Effective sample preparation procedures can clean up the sample and concentrate the analytes of interest. Conventional sample preparation is often the most labor-intensive and time-consuming step in a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method. Introduction of automated 96-well extraction techniques, and advances in sample preparation techniques, have greatly improved the efficiency of sample preparation. 

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