General Information, Appendix, Index
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GENERAL INFORMATION injection device— Equilibration temperature A constant temperature of G1 Physics and Chemistry for inside vial about 809C Equilibration time for 60 minutes inside vial Guideline for Residual Solvents Transfer-line temperature A constant temperature of about 859C and Models for the Residual Carrier gas Nitrogen Solvents Test Pressurisation time 30 seconds Injection volume of sample 1.0 mL 1. Guideline for Residual Solvents (ii) Operating conditions (2) for the head-space sample Refer to the Guideline for Residual Solvents in Phar- injection device— maceuticals (PAB/ELD NotificationNo.307;datedMarch Equilibration temperature A constant temperature of 30, 1998). for inside vial about 1059C Since the acceptable limits of residual solvents recom- Equilibration time for 45 minutes mended in the Guideline were estimated to keep the safety of inside vial patients, the levels of residual solvents in pharmaceuticals Transfer-line temperature A constant temperature of must not exceed the limits, except for in a special case. Phar- about 1109C maceutical manufacturers should assure the quality of their Carrier gas Nitrogen products by establishing their own specification limits or Pressurisation time 30 seconds manufacturing process control limits for residual solvents Injection volume of sample 1.0 mL present in their products in consideration of the limits (iii) Operating conditions (3) for the head-space sample recommended in the Guideline and the observed values in injection device— their products, and by performing the test with the products Equilibration temperature A constant temperature of according to the Residual Solvents Test. for inside vial about 809C Equilibration time for 45 minutes 2. Residual Solvents Test inside vial Generally, the test is performed by using gas chromato- Transfer-line temperature A constant temperature of graphy <2.02> as directed in the Residual Solvents Test about 1059C 2.46 < >. If only the class 3 solvents with low toxic potential to Carrier gas Nitrogen man are present in the products, Loss on Drying Test <2.41> Pressurisation time 30 seconds can be applied in place of gas chromatography, in which case Injection volume of sample 1.0 mL the limit value of residual solvents is not more than 0.5z. The test may also be performed according to the EP 3.2. Models for operating conditions and system suitability method (2.4.24 Identification and control of residual sol- of gas chromatography vents) or the USP method (<467> Residual Solvents). Even in (i) Test conditions (1) (A model described under Proce- this case, description should be in the JP style and the system dure A in the EP and the USP) suitability test should be performed according to the JP rule. Operating conditions— Detector: Hydrogen flame-ionization detector. 3. Models for the operating conditions and system suita- Column: Coat the inside wall of a fused silica tube, 0.32 bility of gas chromatography for residual solvents test mm (or 0.53 mm) in inside diameter and 30 m in length, to The following are typical examples of the operating condi- 1.8 mm(or3mm) thickness with 6z cyanopropylphenyl- tions of gas chromatography for residual solvents test, de- methyl silicon polymer for gas chromatography. Use a guard scribed in the EP and the USP, but these do not necessarily column if necessary. imply that other suitable operating conditions can not be Column temperature: Maintain at 409C for 20 minutes, used. In the operating conditions, generally, items required then increase to 2409Cat109C per minute if necessary, and for the test such as detector, column, column temperature, keep at 2409C for 20 minutes. injection port temperature, detector temperature, carrier Injection port temperature: A constant temperature of gas, flow rate, and time span of measurement should be spe- about 1409C. cified, and in the system suitability, items such as test for re- Detector temperature: A constant temperature of about quired detectability, system performance, and system repeat- 2509C. ability should be specified. The following are several models Carrier gas: Helium. for the operating conditions and the system suitability: Flow rate: 35 cm/second. 3.1. Models for operating conditions for a head-space Split ratio: 1:5. sample injection device (Models described in the EP and the System suitability— USP) System performance: When the procedure is run with the (i) Operating conditions (1) for the head-space sample standard solution under the above operating conditions, the 2135 2136 Physics and Chemistry / General Information JP XVI resolution between the peaks is not less than 1.0. (Note: In System repeatability: When the test is repeated 6 times the case that the number of substances to be tested is two or with the standard solution under the above operating condi- more.) tions, the relative standard deviation of the peak areas of the System repeatability: When the test is repeated 3 times substance to be tested is not more than 15z. with the standard solution under the above operating condi- tions, the relative standard deviation of the peak areas of the substance to be tested is not more than 15z. (ii) Test conditions (2) (A model described under Proce- Inductively Coupled Plasma Atomic dure B in the EP and the USP) Emission Spectrometry Operating conditions— Detector: Hydrogen flame-ionization detector. Inductively coupled plasma (ICP) atomic emission spec- Column: Coat the inside wall of a fused silica tube, 0.32 trometry is a method for qualitative and quantitative analy- mm (or 0.53 mm) in inside diameter and 30 m in length, to sis for the element in the sample specimen, which is nebu- 0.25 mm thickness with polyethylene glycol 20M for gas lized into argon plasma induced by radio frequency power, chromatography. Use a guard column if necessary. by measuring the wavelength and the intensity of the emis- Column temperature: Maintain at 509C for 20 minutes, sion spectra generated by the target element, atomized and then increase to 1659Cat69C per minute if necessary, and excited in the plasma. Argon gas plasma used in this method keep at 1659C for 20 minutes. is characteristic of higher temperature of 6000 ¿ 8000 K and Injection port temperature: A constant temperature of electronic density of 1015 cm－3. about 1409C. When the high energy is externally given to an atom, the Detector temperature: A constant temperature of about orbit transition of the most exterior electron is occurred and 2509C. attained to the excited state. When the excited state of atom Carrier gas: Helium. returns to the basic state, the energy obtained by the excita- Flow rate: 35 cm/second. tion is radiated as a light. The emitted light has an intrinsic Split ratio: 1:5. wave number n and wave length l, attributed to the individ- System suitability— ual element. Assuming the Plank constant h and the light System performance: When the procedure is run with the velocity c, the emitted light energy DE is expressed by the standard solution under the above operating conditions, the following formula. resolution between the peaks is not less than 1.0. (Note: In DE ＝ hn ＝ hc/l the case that the number of substances to be tested is two or more.) Since there are many of combinations of the orbit transi- System repeatability: When the test is repeated 3 times tion energy level of the most exterior electron and the emit- with the standard solution under the above operating condi- ted light energy, usually, there are plenty of spectral lines tions, the relative standard deviation of the peak areas of the emitted from an element, summing up every strong and substance to be tested is not more than 15z. weak emitted lights. However, the number of emitted lights (iii) Test conditions (3) (A model described in Method I of being in the ultra-violet and visible region and having suit- under Other Analytical Procedures in the USP) able detection sensitivity for qualitative and quantitative Operating conditions— analysis are limited to a certain number. Since the atomic Detector: Hydrogen flame-ionization detector. emission spectra give intrinsic wave number or wave length Column: Coat the inside wall of a fused silica tube, 0.53 for the respective element, many of elements contained in a mm in inside diameter and 30 m in length, to 5 mm thickness sample specimen can be identified by the spectroscopic with 5z phenyl-methyl silicon polymer for gas chromatog- analysis of the emitted lights. Furthermore, the quantitative raphy. If necessary use a guard column prepared by coating analysis for an element can also be done by measuring the the inside wall of a fused silica tube, 0.53 mm in inside diam- spectral intensity of the emitted light. eter and 5 m in length, to 5 mm thickness with 5z phenyl- The characteristics of ICP emission spectrometry are sum- methyl silicon polymer for gas chromatography. marized as follows; Column temperature: Maintain at 359C for 5 minutes, ( i ) Microanalysis for plenty of elements is possible. then increase to 1759Cat89C per minute, further increase to ( ii ) Analytical precision is high, since the stable plasma 2609Cat359C per minute if necessary, and keep at 2609C generation can be kept. for 16 minutes. (iii) Linearity of the calibration curve is ensured in the Injection port temperature: A constant temperature of wide range of 4 ¿ 5digit. about 709C. (iv) Multi-element simultaneous analysis is possible. Detector temperature: A constant temperature of about ( v ) Chemical interferences are almost negligible. 2609C. Carrier gas: Helium. The most serious problem in the ICP emission spectro- Flow rate: 35 cm/second. metry is that the spectral interferences are inevitable to this Split ratio: Splitless. analysis, and disturb the analysis for the target element. It System suitability— results from many of emitted spectral lines due to coexisting System performance: When the procedure is run with the elements, because the atomization and excitation of elements standard solution under the above operating conditions, the are done in very high temperature of plasma.