Wednesday, 4 October 2023 13.00 - 17.00 h
In the Pharmacopeial Forum, PF 47(6), a stimuli article entitled "High-Throughput Residual Solvent Analysis Using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS)" was published.
The Stimuli article is available on PF Online. (Please note: a one-time registration is required to access the Pharmacopeial Forum.) The deadline for submitting comments is January 31, 2022.
The United States Pharmacopeia (USP) general chapter <467> Residual Solvents defines the approach to residual solvent analysis. The procedures described in chapter <467> are gas chromatographic techniques using static headspace (HS) for sample introduction and flame ionization detection.
USP chapter <1467> Residual Solvents—Verification of Compendial Procedures and Validation of Alternative Procedures provides general recommendations for verification of procedures of <467> as well as general recommendations for validation of other possible analytical procedures (alternative procedures) to those included in <467>.
As per USP General Notices 6.30 Alternative and Harmonized Methods and Procedures, alternative procedures are permitted when they are fully validated and produce comparable results to the compendial methods or procedures.
According to the authors, the Stimuli article "provides evaluation and validation of selected ion flow tube mass spectrometry (SIFT-MS) as an emerging direct mass spectrometry (DMS) technique. This is an alternative analytical procedure to the procedures in USP <467> for quantification of Class 2 residual solvents based on the recommendations given in [...] <1467> and in International Council for Harmonisation (ICH) Q2(R1) guidelines."
The authors further state that the "Stimuli article focuses on development and validation of a SIFT-MS method for the quantification of 28 Class 1 and 2 residual solvents as an alternative to Procedure C in <467>. Recommended validation characteristics for alternative procedures for residual solvents determinations given in <1467> include specificity, quantitation limit, accuracy, precision, linearity and range, and robustness."
In the Stimuli article, the following aspects are covered:
Based on the results provided, the authors come to the conclusion that "SIFT-MS has the potential of being used as an alternative procedure to those in <467> to demonstrate compliance with acceptance criteria of the chapter. [...] SIFT-MS can be validated for use for the detection and quantitation of most of the residual solvents controlled in USP–NF following the ICH Q2(R1) guidelines, and <1467> recommendations."
The authors further say: "When the validated method is applied to off-line analysis (e.g., in a routine testing laboratory or contract research organization), a throughput of over 200 samples per day is achievable assuming a 24-h operation and that the regular daily calibration samples, blanks, system suitability tests are also run. SIFT-MS has potential to be applied to solvents LTBP in a high-throughput prescreening approach."