1.1 To lay down a procedure for Good chromatography practices in Quality control Laboratory.
2.1 Chemist / Executive – Quality Control – to follow the procedure.
2.2 Group leader / Supervisor – Quality Control to ensure adherence to the procedure.
2.3 Head – Quality Control for implementation and compliance.
- 3.0 PROCEDURE
- 3.1 HPLC MOBILE PHASES:
- Milli – Q water and HPLC grade solvents shall be used for the preparation of mobile phase.
- The mobile phase for the HPLC analysis shall be prepared as per the composition and pH(If any) described in the Standard Testing Procedure (STP).
- Allot the A.R. No. of the sample under analysis as the Reference Number for the mobile phase
- Record the preparation details of the mobile phase in the respective record of analysis or in respective work sheet of the sample under testing.
- Label each mobile phase after its preparation.
- The mobile phase shall be filtered and sonicate and visually check for clarity before use.
- The mobile phase shall be discarded if any precipitation or hazy-ness is observed visually.
- Use the mobile phase within the validity period mentioned in the test procedure. If no validity period is mentioned then use it within 48 hours.
- 3.2 STANDARD PREPARATION:
- The standard preparation shall be made as per the STP, taking into consideration the analyte stability & storage requirement.
- Bracketing Standard shall be handled as per SOP
3.3 SYSTEM SUITABILITY:
- System suitability shall be established as per STP and SOP No.QC097 (Adjustment of Chromatographic conditions).
- System suitability/system precision of the standard shall be established with successive injections.
- The system suitability shall also be verified in the form of system suitability solution or bracketing standard if there is any time gap between the analyses.
- After completion of chromatographic runs of initial system suitability requirement, if there is a delay in running samples at any stage where the time gap from the last established standard run’s acquisition time (of initial system suitability runs or the last bracketing standard, whichever is the latest) is not exceeding 12 hours, then the system shall be continued by running appropriate.
- Bracketing standard first and establishing the system suitability parameters as indicated in the current version of SOP .
- 3.4 SAMPLE PREPARATION:
- All sample preparations shall be prepared as per the method given in the respective STP, taking into consideration the analyte stability & storage requirement.
3.5 CHROMATOGRAPHY ANALYSIS:
- Analysts shall perform analysis of samples after they are qualified and certified as per Standard Operating Procedure
- Follow safety instructions carefully all the time.
- SOPs and logbooks must be maintained at the workplace where it can be easily accessed.
- Update all relevant logbooks concurrently.
- Label all test and standard preparations for all tests with at least details such as A.R. No., solution name and appropriate replicate preparation number wherever is applicable (in a suitable short form incase of space constraint but in an identifiable manner), sign and date with legible marker pen.
- Label vials of GC/ LC analysis using a legible marker pen for as follows XYY, where ‘X’ is the unique quick set or the sample set number (in a suitable short form incase of space constraint but in an identifiable manner) and ‘YY’ is the position at which that vial is to be placed.
- Before starting a sample set, ensure the system suitability (other than %RSD) in single injection mode, make adjustments if necessary for achieving system suitability. Once system suitability is achieved run the complete sample set including the system suitability injection.
- All the single / trial injections shall be processed and documented as disregarded chromatograms.
- The disregarded chromatograms shall not be considered for calculations and shall be stamped or written as “DISREGARDED”. The reasons for disregarding of the chromatogram shall be documented.
- The disregarded chromatogram shall be filed along with the test chromatograms
- During chromatographic analysis, use blank determinations at appropriate intervals to confirm and ensure baseline stability verification and carry over contaminations.
- Label all known peaks such as peak due to blank, placebo, known impurities and analyte in chromatograms obtained with blank, system suitability, first standard run of the RSD determination sequence, first trial of sample and each bracketing standard.
- Attach all relevant analytical raw data obtained from instruments such as High Performance Liquid Chromatograph, Gas Chromatograph to the work sheet.
- Retain all solutions used in the analysis for tests to determine unit dose quality such as Uniformity of Dosage Unit, Content Uniformity, Dissolution and equipment cleaning
- samples for content of active ingredient (store on bench top or in refrigerator as mentioned in the standard test procedure based on the solution stability) until analytical results are determined so as to facilitate Incident / Out Of Specification investigation.
- Report all incidents and failures to the supervisor as soon as possible and follow instructions.
- If any measured bracketing standard is not meeting the acceptance criteria, raise incident as per the current version of the and determine the status of result based on the disposition comments made by Head QA.
- After completion of chromatographic runs of initial system suitability requirement, if there is a stoppage of the system due to any reasons, then raise a ‘Incident’ as per the SOP (Reporting of Incidents in Quality control Laboratory). If the time gap from the last established standard run’s acquisition time (of initial system suitability runs or the last bracketing standard, whichever is the latest) is not exceeding 12 hours, then the system shall be restarted (re run) by running appropriate Bracketing standard first and establishing the system suitability parameters as indicated in the SOP Bracketing Standards and any other system suitability parameters if any instructed by the supervisor. If the stoppage is due to removal of Column, change or addition of freshly prepared mobile phase to the existing volume, then the analysis shall be restarted and continued of after establishing initial system suitability parameters as per respective Analytical Method or STP.
- All the digits appearing on the chromatogram shall be taken as such for calculation.
- Reprocessing of chromatograms, if necessary, at a later date/time shall be documented with reason(s) for reprocessing.
- GC – Gas chromatography.
- HPLC – High performance liquid chromatography.
- STP – Standard Testing Procedure.
- QA – Quality Assurance.
- A.R. No. – Analytical Reference Number.
- LC – Liquid chromatography.
- OOS – Out of specification.
- SOP – Standard Operating Procedure.
- QC – Quality control.
5.1 Adjustment of chromatographic conditions
5.2 Bracketing of Standards during content Uniformity, Assay, Dissolution, Related substances, Organic volatile impurities and Residual solvents.
5.3 Qualification of analyst in quality control
5.4 Reporting of incidents in quality control laboratory