STANDARD OPERATING PROCEDURE Operating and Calibration Procedure for TOC Analyzer

	STANDARD OPERATING PROCEDURE
	Department: Quality Control	SOP No.: QC/
Operating and Calibration Procedure for TOC Analyzer		Effective Date:
		Review Date:
		Page No.:

1.0            OBJECTIVE:

1.1                            To lay down a procedure for operation and calibration of TOC analyzer.

2.0            SCOPE:

2.1                            This SOP is applicable to the TOC Analyzer located in Quality Control department at  Pharma Private Limited.

ID.No: 

3.0            RESPONSIBILITY:  

3.1                            QC Chemist/Microbiologist – Responsible for operation and calibration of the instrument.

3.2                 Section In-charge - To review the procedure and reports.

3.3                 QC Head – Responsible for implementing the procedure.

3.4                 QA Head – Overall compliance.

4.0            PROCEDURE:

4.1                 Operating Procedure:

4.1.1                      Switch on the power and mains of the instrument and check the following before operating the equipment.

4.1.2                      The pressure of the zero air/nitrogen gas should be within the range of 44 – 87 psi (If not turn the key cylinder and adjust the pressure).

4.1.3                      The level of water in the humidifier should be between the lower level and the upper level marks. (if not, open the humidifier and fill water up to the level).

4.1.4                      The rinse water bottle is filled to above the 2L mark on the bottle. The tip of the rinse tube reaches nearly to the bottom of the rinse water bottle.

4.1.5                      Check &fill 25% of phosphoric acid in the phosphoric acid bottle kept in                         left side of the TOC analyzer (when ever required).

4.1.6                      Check &fill 25% 2N hydrochloric acid in the hydrochloric acid bottle and             keep it in the left side of the TOC analyzer (whenever required).

4.1.7                      After completion of above mentioned procedure press the power button                       on the front panel of the instrument.

4.1.8                      Then the initial display shows initializing on the display.

4.1.9                      Setting of carrier gas flow rate:

4.1.9.1                Open the front door of the instrument

4.1.9.2                Turn the carrier gas flow adjustment knob, adjust the flow rate to 150mL/min.

4.1.9.3                After all adjustments check background monitor by pressing F3 key, and check the following parameters to be used for start the  analysis.

4.1.9.4                Check the air pressure about 200 kilopascal and flow rate is about 150mL/min. A small window comprising of the Background Monitor will appear on the screen

4.1.9.5                The Background Monitor consist of the following parameters

4.1.9.5.1          Furnace: 680ºc

4.1.9.5.2          Dehumidifier: 1.4

4.1.9.5.3          Baseline Position: OK

4.1.9.5.4          Baseline Fluctuation: OK

4.1.9.5.5          Baseline Noise: OK

4.1.9.6                After attaining the all parameters, green light will flash to indicate the system ready for analysis.

4.1.9.7                Then press return key (F1) to go back to main screen.     

4.1.10                  Measuring of sample:  

4.1.10.1            Press ASI key followed by Measure Sample key.

4.1.10.2            The measurement setting screen is displayed. Then enter required values as given below.

4.1.10.3            Sample name: Enter the sample name (max 16 characters) by using numeric keys (use shift button for alphabets), then press enter key.

4.1.10.4            Vial number: Move the cursor from the sample name to vial number and then enter the vial no 1 to 8 and press enter key.

4.1.10.5            Press F5 key the display shows the following parameters and use ↓ key to move   the cursor to each parameter.

4.1.10.5.1      Calibration curve: Sets the calibration curve to be used (from two point calibration) and press enter key.

4.1.10.5.2       Minimum Number of injections: Enter the Minimum number of sample analysis injections (3) to be performed and press enter key.

4.1.10.5.3      Maximum number of injections: Enter the maximum number of sample injections (5) to be performed.

4.1.10.5.4      Standard deviation: Enter the standard deviation value (0.5%) and press enter key.

4.1.10.5.5      Coefficient variation: enter the coefficient variation value (3%) and press enter key.

4.1.10.5.6      Dilution factor: Enter the dilution factor (1) and press enter key.               

4.1.10.5.7      Injection volume: Given by system automatically (816 µL)

4.1.10.5.8      Acid addition ratio: Enter the acid addition ratio (0.5%) and press enter key.

4.1.10.5.9      Sparge time: Enter the sparge time (0.5 min) and press enter key.

4.1.10.6            After setting the parameters press enter and then next key.

4.1.10.7            Keep the sample in respective vial and press start.

4.1.10.8            After analysis is completed, display shows Area and ppb.

4.1.10.9            After completion of analysis process the press the stand by button then select power off by using F5 button .Then press Execute (F6 key). Now the system asks for confirmation, press Yes (F6 Key). The system automatically shut down. (App.20 min)

4.1.10.10        Then put off main switch and main gas supply.

4.2                 Calibration procedure:

4.2.1                      Two point calibration: By Sucrose solution

4.2.1.1                Preparation of Sucrose Standard stock solution: Weigh accurately 11.9 mg of sucrose which is previously dried at 105°C for 3 hours, and dissolve and diluted it to 100 mL with zero water (50ppm). Dilute 1 mL of this solution to 100 mL with zero water. (0.50 mg of carbon per liter or 500 ppb).

4.2.1.2                Measure standard response for blank and 500 ppb solution.

4.2.1.3                Blank: Zero water (100ppb).

4.2.1.4                Calibration Procedure:

4.2.1.4.1          Press data report (F6) from initial display.

4.2.1.4.2          Press Cal. Curve list (F6).

4.2.1.4.3          Select TC2 from Cal. Curve list by using UP and DOWN arrow

4.2.1.5                Press edit key (F6)

4.2.1.6                Change curve shift status from origin to none by pressing F4 Key.

4.2.1.7                Press OK (F6)

4.2.1.8                Press Return (F1)

4.2.1.9                Keep the Blank (Zero Water) in Vial no.1

4.2.1.10            Keep the sucrose solution (500ppb) in vial no.2

4.2.1.11            Press ASI button

4.2.1.12            Press Cal Button

4.2.1.13            Press 2 followed by enter now display will show two calibration points.

4.2.1.14            Then press Next button for two times.

4.2.1.15            Now the display will show “Set Sample and Press START button”

4.2.1.16            Press Start button to start the calibration.

4.2.1.17            After completion of two point calibration change the shift  option from none to origin by following the point no. 4.2.1.4.1 to 4.2.1.4.7

4.2.2                      Single point calibration (System Suitability): By 1, 4- Benzoquinone solution

4.2.2.1                Preparation of 1, 4- Benzoquinone solution: Dissolve 15 mg of 1, 4- Benzoquinone into 200 mL of zero water and diluted 1 mL of this solution to 100 mL with zero water. (0.50 mg of carbon per liter or 500 ppb)

4.2.2.2                Measure standard response for 500 ppb solution.

4.2.2.3                Note: To perform single point calibration, two point calibration shall be performed first.

4.2.2.4                Calibration Procedure:

4.2.2.4.1          Follow procedure as mentioned in two point calibration  4.2.1.1 to 4.2.1.17   

4.2.2.4.2          Press ASI key followed by Measure Sample key.

4.2.2.4.3          Now the measurement setting screen will displayed. Then enter required values as given below.

4.2.2.4.4          Sample name: Enter the sample name (1, 4 Benzoquinone) by using numeric keys (use shift button for alphabets), then press enter key.

4.2.2.4.5          Vial number: Move the cursor from the sample name to vial number and then enter the vial no 1 to 8 and press enter key.

4.2.2.4.6          Press F5 key (NPOC) the display shows the following     parameters and use ↓ key to move the cursor to each parameter.

4.2.2.4.7          Calibration curve: Sets the calibration curve to be used (from two point calibration) and press enter key.

4.2.2.4.8          Minimum Number of injections: Enter the Minimum number of sample analysis injections (3) to be performed and press enter key.

4.2.2.4.9          Maximum number of injections: Enter the maximum number of sample injections (5) to be performed.

4.2.2.4.10      Standard deviation: Enter the standard deviation value (0.5%) and press enter key.

4.2.2.4.11      Coefficient variation: enter the coefficient variation value (3%) and press enter key.

4.2.2.4.12      Dilution factor: Enter the dilution factor (1) and press enter key.

4.2.2.4.13      Injection volume: Given by system automatically (816 µL).

4.2.2.4.14      Acid addition ratio: Enter the acid addition ratio (0.5%) and press enter key.

4.2.2.4.15      Sparge time: Enter the sparge time (0.5 min) and press enter key.

4.2.2.4.16      After setting the parameters press enter and then Next key for two times.

4.2.2.4.17      Display will show “Set Sample and Press START button”

4.2.2.4.18      Keep the sample in respective vial and press start.

4.2.2.4.19      Press Start button to start the calibration.

4.2.2.4.20      After analysis is completed, display shows Area and ppb.

4.2.2.4.21      Formula for manual calculation of recovery:

                                                                               Rss - Rw

                                           % Recovery = ---------------- X 100

                                                                     Rs – Rw

                                           Where,    Rss    =   Mean area of 1, 4 Benzoquinone

                                                           Rw    =   Mean area of Zero Water

                                                                      Rs      =   Mean area of Sucrose

4.2.3                      Four point calibration: By Potassium hydrogen phthalate solution

4.2.3.1                Preparation of PHP Standard stock solution: Weigh accurately                            0.2125 g of potassium hydrogen phthalate, dissolve and dilute with 100 mL zero water (1000 ppm carbon stock solution).  Dilute 1 mL of this solution to 100 mL with zero water. (10 ppm carbon stock solution)

4.2.3.2                Further dilutions like 250 ppb, 500 ppb, and 1000 ppb shall be prepared though auto dilution by instrument. Here dilution factor is applied automatically by the instrument that is 40, 20, & 10 respectively.

4.2.3.3                Measure standard response for blank, 250 ppb, 500 ppb and 1000 ppb.

4.2.3.4                Blank: Zero water (100ppb).

4.2.3.5                Calibration Procedure:

4.2.3.5.1          Press data report (F6) from initial display.

4.2.3.5.2          Press Cal. Curve list (F6).

4.2.3.5.3          Select the 1000ppb calibration curve from Cal. Curve list by using UP and DOWN arrow

4.2.3.5.4          Press edit key (F6)

4.2.3.5.5          Change curve shift status from origin to none by pressing F4 Key.

4.2.3.5.6          Press OK (F6)

4.2.3.5.7          Press Return (F1)

4.2.3.5.8          Keep Blank (zero water) in Vial no.1 and PHP solution in vial No. 2

4.2.3.5.9          Press ASI button followed by Cal button

4.2.3.5.10      Select the calibration curve from calibration curve list by pressing 1.

4.2.3.5.11      Then press “Next” button for two times.

4.2.3.5.12      Display will show “Set Sample and Press START button”

4.2.3.5.13      Press “Start” button to start the calibration.

4.2.3.5.14      After analysis is completed, display shows Area and ppb.

4.2.3.5.15      After completion of two point calibration change the shift option from none to origin by following the point no.4.2.3.5.1 to4.2.3.5.7.

4.2.3.6                Acceptance criteria:

4.2.3.6.1          % Recovery of 1, 4 Benzoquinone is 85 % to 115 %.

4.2.3.6.2          Standard deviation is NMT 0.5.

4.2.3.6.3          Coefficient of variation is NMT 3.0 %.

4.2.3.6.4          Either standard deviation or coefficient of variation shall meet.

4.3                            After usage of instrument, the usage details shall be entered in Annexure IV.

4.4                 Frequency:

4.4.1                      Two point calibration: Weekly.

4.4.2                      Single point calibration (System Suitability): Monthly ± 3days.

4.4.3                      Four point calibration: Quarterly ± 7 days.

4.5                            If TOC analyzer is failed to meet an acceptance criteria of calibration, then out of calibration shall be investigated as per current version of SOP QA/.

4.6                 Precautions:

4.6.1                      Do not switch on the instrument without supply of zero air.

4.6.2                      External drain tubing connected to the waste port on the right side of the instrument does not touch the surface of the liquid in the waste container.

4.6.3                      Do not switch off the instrument directly (except Emergency).

4.6.4                      All glassware used for TOC analysis shall be cleaned as per QC/

4.6.5                      At sample collection point wash bottles with purified water 2 to3 times by filling top without  leaving any air gap in sampling bottle.

4.6.6                      Close the cap and seal it with para film.

5.0           Abbreviations:

ppm: parts per million	NMT: Not More Than
ppb: parts per billion	QC: Quality Control
SOP: Standard Operating Procedure	IC: Inorganic Carbon
TOC: Total Organic Carbon	QA: Quality Assurance
NPOC: Non-Purgeable Organic Carbon