Chromatography
Equivalent GC systems performance for regulatory method compliance and validation
Giulia Riccardino, David Lee, and Cristian Cojocariu, Thermo Fisher Scientifi c, Runcorn, UK
Migration of methods between laboratories or from one analytical system to another when replacing technologies such as gas (GC) or liquid chromatographic (LC) system, either as a result of updating analytical equipment or changing from one supplier to another, could be a time consuming and diffi cult task. The instruments used in analytical laboratories are diverse and can belong to various brands. Often the same analytical method is used on instruments that are manufactured by different vendors with the expectation that the performance is equivalent.
As part of the method transfer and validation, federal and governmental agencies, such as the United States Food and Drug Administration (US-FDA), and the European Medicines Agency (EMA) released specifi c guidelines [1,2]. Moreover, the USP Chapter 621 of the current United States Pharmacopeia has suitability procedures to test analytical methods and demonstrate equivalency when transferring them from one system to another [3]. This is also applicable for GC methods where strict chromatographic separation criteria are defi ned.
In this paper, two examples of how the Thermo Scientifi c™ TRACE™ 1300 and 1600 Series Gas Chromatograph systems perform with typical, well-known GC methods for pharmaceutical and food industry are detailed, demonstrating the compatibility with common consumables such as liners and capillary columns, simplifying the method portability assuring equivalency of the analytical performance. The instrument conditions are not included herein. Please refer to the full paper (WP-74062) for information on instrument conditions.
Residual solvent analysis in pharmaceutical products according to USP <467> method Introduction
Solvents are widely used in the synthesis of pharmaceutical products, substances and excipients. To ensure patients’ safety, the International Conference on Harmonization (ICH) [4] and the United States Pharmacopeia (USP)[5] have published some guidelines to set the acceptable limits and to support the assessment of the residual solvents used during the production and purifi cation processes. Residual solvents (RS) have low boiling points and thermal stability therefore they can be determined using headspace-gas chromatography (HS-GC) coupled to fl ame ionisation detection.
The workfl ow for residual solvent assessment is reported using a simplifi ed schematic in Figure 1. When the residual solvents that are likely to be present are known, they can be determined using a limit test, such as Procedure A or Procedure B, or by a quantitative test, such as Procedure C. When the residual solvents are not known, then a screening test using Procedure A must be used. If the article does not meet the acceptance criteria of Procedure A, then Procedure B must be used to demonstrate compliance. If the article does not meet the criteria using Procedure A and Procedure B, then Procedure C must be used to quantify the residual solvents present in the article.
Results and discussion Procedure A - Screening of unknown residual solvents
Stock, standard and test solutions were prepared according to the USP <467> method. An over-the-counter acetylsalicylic acid (dispersive aspirin, 75 mg) was purchased locally and analysed according to the USP <467> workfl ow in Figure 1.
System suitability criteria for sensitivity (peak-to-peak (PtP) signal-to-noise ratio (S/N)) and chromatographic resolution (Rs
) were met with:
• S/N > 5:1 for 1,1,1-trichloroethane in Class 1 standard solution • S/N >3:1 for all peaks in Class 1 system suitability solution (Figure 2) • Rs
between acetonitrile/dichloromethane >1 in Class 2A standard solution (Figure 2).
responses obtained for the un-spiked sample were lower than the corresponding peaks in Class 1 and Class 2 standard injections. According to the regulation, the test solution met the requirements for residual solvent content with no other actions required.
A streamlined method transfer from a different HS-GC system using the Valve-and-Loop headspace technology is ensured by the consistency of the method parameters. The name to report the method parameters may differ within different brands, especially for the headspace autosampler. The equivalency of the parameters is clearly explained in a previous published white paper [6].
The innovative system design with direct connection between the gas chromatograph and the autosampler combined with the high inertness and the precise temperature and fl ow controls of the TRACE 1310 Gas Chromatograph allowed for an effi cient chromatographic process ensuring Gaussian peak shapes with average asymmetry factor (As
) of 1.2. Peak
Figure 1. Simplifi ed diagram of the analytical workfl ow used for residual solvent assessment. *Equivalent or better performance with the Thermo Scientifi c TRACE 1600 Series Gas Chromatograph systems
acetonitrile/dichloromethane.
Figure 2. Chromatographic separation of class 1, class 2A and class 2B residual solvents with annotated compound number as well as chromatographic resolution (Rs
) for critical pair
LAB ASIA - APRIL 2022
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52
