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User Benefits Application News GC-2010 Pro offers advanced capabilities for the detection of EG and DEG contamination in the raw materials (glycerin, propylene glycol and sorbitol) used for manufacturing medicinal syrup. The configuration proposed in the application news exceeds the requirement specified in the USP monographs. GC-2010 Pro coupled with the AOC-20i+s Plus autosampler can obtain highly reproducible results using the proposed workflow. Introduction Glycerin, propylene glycol (PG) and sorbitol are commonly used as excipients in medicinal syrup during formulation. Their global supply chains are vital to both the pharmaceutical and consumer healthcare industries, as these 3 raw materials are widely used by these industries. Ensuring the safety and quality of these raw materials in the supply chains is a significant challenge to the authorities, as evidenced by some incidents, such as reports of deaths in Indonesia, Gambia [1] and Uzbekistan [2] due to the contamination of ethylene glycol (EG) and diethylene glycol (DEG) in medicinal syrup. Several companies in Indonesia have been implicated for their involvement in the distribution of contaminated raw materials to pharmaceutical companies [3]. To prevent the recurrence of contaminated medicinal syrup from reaching the general public, more stringent multi-level Quality Control (QC) and checks must be in place during the manufacturing of the medicinal syrup. Figure 1 displays the suggested checks that could be implemented. The scope of the QC check must start from the manufacturing of raw materials till the end of the finished products. Following the release of two applications news for the detection of EG and DEG in finished medicinal syrup [4,5], this application news is published to show determination of ethylene glycol (EG) and diethylene glycol Figure 2. Shimadzu’s GC-2010 Pro with AOC™-20i+s Plus and PEAK Scientific’s Precision SL 100 Hydrogen Generator Analysis of Ethylene Glycol and Diethylene Glycol in Glycerin, Propylene Glycol and Sorbitol via GC-FID in Accordance with USP Monographs Gas Chromatograph GC-2010 Pro Puah Perng Yang 1 , Yanwar Pratama Putra 2 , Amih Maulida 2 , Dewi Arba’ina 2 , Jenita Salsalina 2 , Annisa Salsabila 2 , Chia Chee Geng 1 , Cynthia Melanie Lahey 1 and Jackie Jackie 1 1 Shimadzu (Asia Pacific) Pte Ltd, Singapore, 2 PT Ditek Jaya, Indonesia Figure 1. The scope covered by the application news released earlier and the gap to be addressed in this application news (DEG) in pharmaceutical raw materials: glycerin, propylene glycol (PG) and sorbitol. This was performed in accordance with the United States Pharmacopoeia (USP) monographs, using a gas chromatograph with flame ionization detector. Measurement Conditions This study employed Shimadzu’s GC-2010 Pro coupled with the AOC-20i+s Plus autosampler with flame ionization detector (FID), while PEAK Scientific’s Precision SL 100 Hydrogen Generator was utilized to generate hydrogen for FID (Figure 2). The analytical conditions utilized for the analysis, in accordance with the method outlined by the USP [6,7,8], are provided in Table 1. A notable modification was implemented to the injection volume used for analyzing glycerin and PG. The injection volume was reduced from 1.0 µL to 0.5 µL to avoid the risk of contaminating the GC system. Additionally, in the sorbitol analysis, the final column oven temperature program was adjusted to 270 °C (instead of 300 °C) due to the column- recommended specification. USP Requirements USP has established specific compendia tests for detecting contaminants such as EG and DEG in glycerin, PG and sorbitol. The analytical methods specified in the USP monographs are based on GC-FID. The criteria to be met, as specified in the monographs are stated in Table 2. The gap to be addressed in this application news ・Raw material ・In-process testing ・Finished product testing before released ・Finished product testing ・ OMCL (Europe) ・ FDA (US) ・ HSA (Singapore) ・ BPOM (Indonesia) ・Finished product monitoring ・ OMCL (Europe) ・ FDA (US) ・ HSA (Singapore) ・ BPOM (Indonesia) ・ Manufacturing QC site During Manufacturing Prior to Market Release After Market Release
Application News System Configuration Raw Material Glycerin Propylene Glycol (PG) Sorbitol GC System GC-2010 Pro Auto Injector AOC ™ -20i+s Plus Syringe 5 µl syringe [P/N: 221-75173] Column SH-624 (USP G43 phase) 30 m x 0.53 mm I.D. x 3.0 µm df [P/N: 221-75865-30] SH-624 (USP G43 phase) 30 m x 0.53 mm I.D. x 3.0 µm df [P/N: 221-75865-30] SH-1701 (USP G46 phase) 15 m x 0.32 mm I.D. x 0.25 µm df [P/N: 221-75780-15] Injector Parameters Injection Mode Split mode (using deactivated split liner with glass wool) (Split ratio = 10) Injector Temperature 220 °C 220 °C 240 °C Injection Volume 0.5 µL 0.5 µL 1.0 µL Carrier Gas Helium Flow Control Mode Linear velocity Column Flow Rate 4.5 mL/min 4.5 mL/min 3.0 mL/min GC Oven Parameters Column Oven Temperature Program Initial temp. 100 °C (hold for 4 min) - Increase to 120 °C with a rate of 50 °C/min (hold for 10 min) - Increase to 220 °C with a rate of 50 °C/min (hold for 6 min) Initial temp. 100 °C (hold for 4 min) - Increase to 120 °C with a rate of 50 °C/min (hold for 10 min) - Increase to 220 °C with a rate of 50 °C/min (hold for 6 min) Initial temp. 70 °C (hold for 2 min) - Increase to 270 °C with a rate of 50 °C/min (hold for 5 min) FID Parameter Detector Temperature 250 °C 250 °C 300 °C Table 1. System configuration and analytical conditions for the analysis of EG and DEG in glycerin, propylene glycol and sorbitol sorbitol raw material to a 25-mL volumetric flask. Then, 1.0 mL of diluent was added, and the mixture was vortexed for 3 minutes. The remaining diluent was added in three equal portions, with 3-minute vortexing upon each addition, until the mark of the volumetric flask was reached. A portion of the supernatant layer was passed through a 0.45-µm nylon filter. The initial 2 mL filtrate was discarded, and the remaining filtrate was collected for sample analysis. (Note: acetone was used for the precipitation of sorbitol). Preparation of Spiked Sample Spiked Sample Solution Preparation To simulate a sample that exceeds the USP acceptance criteria, USP EG and USP DEG were intentionally spiked into the raw material samples. Glycerin Spiked Sample Glycerin spiked sample was prepared in methanol with a final concentration of 50 mg/mL glycerin raw material, 0.10 mg/mL 2,2,2-trichloroethanol (IS), 0.055 mg/mL USP EG and 0.055 mg/mL USP DEG. PG Spiked Sample PG spiked sample was prepared in methanol with the final concentration of 50 mg/mL PG raw material, 0.10 mg/mL 2,2,2- trichloroethanol (IS), 0.055 mg/mL USP EG and 0.055 mg/mL USP DEG. Sorbitol Spiked Sample Diluent was first prepared by mixing acetone and water (96:4). Sorbitol spiked sample solution was prepared by adding 2.0 g of sorbitol raw material to a 25-mL volumetric flask. USP EG and USP DEG were then spiked into the sample, each at a final concentration of 0.088 mg/mL. Then, 1.0 mL of diluent was added and the mixture was vortexed for 3 minutes. The remaining diluent was added in three equal portions, with 3-minute vortexing upon each addition, until the mark of the volumetric flask was reached. A portion of the supernatant layer was passed through a 0.45 µm nylon filter. The initial 2 mL filtrate was discarded, and the remaining filtrate was collected for sample analysis. Preparation of Standard Standard solution preparation EG, DG, glycerin and PG of USP grade were prepared in accordance with USP monographs. Glycerin Standard Glycerin standard solution was prepared in methanol with a final concentration of 2.0 mg/mL USP glycerin, 0.10 mg/mL 2,2,2-trichloroethanol (Internal Standard, IS), 0.05 mg/mL USP EG and 0.05 mg/mL USP DEG. PG Standard PG standard solution was prepared in methanol with a final concentration of 2.0 mg/mL USP PG, 0.10 mg/mL 2,2,2- trichloroethanol (Internal Standard, IS), 0.05 mg/mL USP EG and 0.05 mg/mL USP DEG. Sorbitol Standard Diluent was first prepared by mixing acetone and water (96:4). Sorbitol standard solution was prepared in diluent with a final concentration of 0.08 mg/mL USP EG and 0.08 mg/mL USP DEG. Preparation of Sample Sample Solution Preparation Raw material samples for glycerin, PG, and sorbitol were prepared as per USP monographs. Glycerin Sample Glycerin sample was prepared in methanol with a final concentration of 50 mg/mL glycerin raw material and 0.10 mg/mL 2,2,2-trichloroethanol (IS). PG Sample PG raw material sample was prepared in methanol with a final concentration of 50 mg/mL glycerin raw material and 0.10 mg/mL of 2,2,2-trichloroethanol (IS). Sorbitol Sample Diluent was first prepared by mixing acetone and water (96:4). Sorbitol raw material sample was prepared by adding 2.0 g of
Application News 1.00 1.25 1.50 1.75 2.00 2.25 2.50 2.75 3.00 3.25 min 0 5000 10000 15000 20000 25000 30000 35000 40000 uV (c) EG DEG Impurity peak from acetone 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0 min 0 500 1000 1500 2000 2500 3000 3500 4000 uV EG 2,2,2-trichloroethanol (IS) DEG (a) 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 14.0 min 0 500 1000 1500 2000 2500 3000 3500 4000 uV EG PG (b) 2,2,2-trichloroethanol (IS) DEG Figure 3. Standard chromatograms of ethylene glycol (EG) and diethylene glycol (DEG) in (a) glycerin standard, (b) PG standard and (c) sorbitol standard Thus, in addition to the criteria in Table 2, the following would be determined for glycerin and PG methods: • %RSD of EG and DEG peak response ratios • Signal-to-noise ratio of EG and DEG peak response at 0.1% Glycerin Standard Figure 3a depicts the chromatogram for glycerin standard. The peaks observed are well-separated among the analytes of interest. RRT of EG, IS, DEG and glycerin were reported as 0.3, 0.6, 0.8 and 1.0, respectively (Table 3). The observed RRT was consistent with the reference RRT in the USP monograph. The average resolution between DEG and glycerin peaks was reported as 15.9 (Table 4), thus fulfilling the USP requirement that the resolution between those 2 peaks must be greater than 1.5. Results and Discussion System Suitability The System Suitability Test (SST) requirements are summarized in Table 2. The SST is based on the specific peak resolution between the analytes mentioned in Table 2. Glycerin and PG methods use a wide bore column of 0.53 mm ID (Table 1), resulting in low column head pressure. Using the analytical conditions in Table 1, methanol (diluent for glycerin and PG) produces a high expansion volume at low pressure. This could create backflash which potentially contaminates the instrument. Hence, the injection volume was decreased to 0.5 µl for glycerin and PG analyses. USP states that when the injection volume is reduced, special attention needs to be given to these [9]: • Repeatability of the peak response • The impurities (EG and DEG) should be reliably detected at the concentration limit USP Requirements Glycerin Propylene Glycol (PG) Sorbitol Resolution ≥ 1.5 between DEG and glycerin ≥ 5 between EG and PG ≥ 30 between EG and DEG Acceptance Criteria • Peak response ratio of EG or DEG in the sample is not more than the peak response ratio in the standard* (which corresponds to ≤ 0.10% of EG or DEG in the sample) • RT + of glycerin peak in sample solution should correspond to the RT + of glycerin peak in standard • Peak response ratio of EG or DEG in the sample is not more than the peak response ratio in the standard* (which corresponds to ≤ 0.10% of EG or DEG in the sample) • RT + of PG peak in sample solution should correspond to RT + PG peak in standard • Peak area of EG or DEG in sample is not more than the peak area of EG or DEG in standard (which corresponds to ≤ 0.10% of EG or DEG in the sample) Table 2. USP requirements for the analysis of glycerin, propylene glycol and sorbitol *Refer to Calculation section for the determination of peak response ratio. + Denotes retention time. Glycerin
Application News Table 5. Repeatability (n=5) of the glycerin, PG and sorbitol standards Standard Solution Glycerin Standard PG Standard Sorbitol Standard Injection Peak Response Ratio (EG/IS # ) S/N + (EG) Peak Response Ratio (DEG/IS # ) S/N + (DEG) Peak Response Ratio (EG/IS # ) S/N + (EG) Peak Response Ratio (DEG/IS # ) S/N + (DEG) Peak Area (EG) Peak Area (DEG) 1 0.913 147.55 0.819 27.62 0.856 112.89 0.718 28.57 44,525 45,205 2 0.866 87.18 0.768 25.62 0.846 93.07 0.716 37.26 43,719 44,689 3 0.914 125.46 0.770 25.88 0.858 91.55 0.741 43.22 44,537 45,205 4 0.877 95.85 0.788 23.57 0.848 86.28 0.734 26.34 44,391 45,309 5 0.897 129.92 0.794 28.15 0.861 87.68 0.718 27.60 44,630 45,360 Average 0.893 117.19 0.788 26.17 0.854 94.29 0.725 32.60 44,361 45,154 Std. Dev.* 0.021 0.021 0.006 0.011 368.468 268.174 %RSD 2.39% 2.65% 0.77% 1.57% 0.83% 0.59% Table 3. Relative retention times (RRT) and retention times (RT) of the glycerin, PG and sorbitol standards Standard Solution Glycerin Standard (RRT*) PG Standard (RRT*) Sorbitol Standard (RT + )/min Injection EG IS # DEG Glycerin EG PG IS # DEG EG DEG 1 0.3 0.6 0.8 1.0 0.9 1.0 1.7 2.5 1.2 3.2 2 0.3 0.6 0.8 1.0 0.9 1.0 1.7 2.5 1.2 3.2 3 0.3 0.6 0.8 1.0 0.9 1.0 1.7 2.5 1.2 3.2 4 0.3 0.6 0.8 1.0 0.9 1.0 1.7 2.5 1.2 3.2 5 0.3 0.6 0.8 1.0 0.9 1.0 1.7 2.5 1.2 3.2 USP reference ¤ 0.3 0.6 0.8 1.0 0.8 1.0 1.7 2.4 DEG elutes after EG Standard Solution Glycerin Standard PG Standard Sorbitol Standard Injection Resolution (between DEG & Glycerin) Resolution (between EG & PG) Resolution (between EG & DEG) 1 15.8 7 54 2 16.0 7 53 3 15.9 7 54 4 15.9 7 54 5 16.1 7 54 Average 15.9 7 54 USP Requirement ≥ 1.5 ≥ 5 ≥ 30 Table 4. System Suitability Requirement for Resolution of the glycerin, PG and sorbitol standards *Denotes Standard Deviation. # Denotes Internal Standard. + Denotes Signal-to-Noise Ratio *Denotes Relative Retention Time. + Denotes Retention Time. # Denotes Internal Standard. ¤ Relative retention time provided in USP monograph for reference purpose. USP requirement (resolution between those 2 peaks should be not less than 5). An average peak response ratio to the internal standard, for EG and DEG obtained was 0.854 (EG/IS) and 0.725 (DEG/IS) respectively (Table 5). For the repeated injections (n=5), %RSD of 0.77% and 1.57% were observed for EG/IS and DEG/IS, respectively (Table 5). The average S/N ratios for the EG and DEG peaks were 94.29 and 32.60, respectively. These results demonstrate high precision and reliability in detecting EG and DEG impurities. Sorbitol Standard Figure 3c depicts the chromatogram for the sorbitol standard. The peaks of interest were well-resolved as shown. An unknown peak observed at around RT 1.78 min was attributed to the impurities intrinsically present in the acetone used. The RT of EG and DEG was observed at 1.2 and 3.2 min respectively (Table 3). The average (n=5) resolution of the peak between EG and DEG obtained was observed to be 54 (Table 4). This result obtained exceeds the USP requirement by almost twice (Table 2). It was observed that the average (n=5) peak areas obtained were 44361 and 45154 for EG and DEG respectively (Table 5). %RSD for the repeated injections (n=5) obtained was observed to be 0.83% and 0.59% for EG and DEG peak areas respectively (Table 5), demonstrating that a high degree of precision was successfully achieved. The repeatability of the experiment was assessed by analyzing five replicate injections (n=5) of the glycerin standard. The average peak response ratio of EG to IS (EG/IS) was observed to be 0.893 and 0.788 (Table 5) for peak response ratio of DEG to IS (DEG/IS). Highly precise repeatability was observed from the repeated injections. For EG/IS and DEG/IS ratios, %RSD of 2.39% and 2.65% were obtained, respectively (Table 5). The average signal-to-noise (S/N) ratios for the EG and DEG peaks were 117.19 and 26.17, respectively. Given the low %RSD and the high S/N ratios, the method reliably detects EG and DEG impurities at the limit of 0.10%. PG Standard Figure 3b depicts the chromatogram for the PG standard. The peaks were well-resolved among the analytes of interest, with the RRT of EG, PG, IS and DEG reported as 0.9, 1.0, 1.7 and 2.5, respectively (Table 3). It is worth noting that, as a reference, the RT for PG in the USP monograph was stated to be 4 min. The RT for PG was observed to be 4.87 min in our experiment. Thus, the observed RRTs for EG and DEG obtained in our experiment were off by 0.1 from the value provided in the USP monograph (Table 3). Such minor deviation is within expectation due to the observed column-to-column variations. The average resolution between EG and PG peaks was found to be 7 (Table 4), thus satisfying the
Application News Figure 4. Chromatograms of (a) glycerin sample, (b) PG sample and (c) sorbitol sample Sorbitol Sample Figure 4c depicts the chromatogram for the analysis of the sorbitol raw material. DEG peak was not detected, but EG peak was detected in the sample. The average peak area for EG in the sorbitol sample was less than 2200 (Table 7). This result indicates that the detected peak area of EG in the sorbitol sample was lower than the average EG peak area observed in the sorbitol standard analyzed earlier (44361). As the peak areas of EG and DEG in the sorbitol sample were not more than the peak areas in the standard, it can be concluded that this sorbitol sample complies with the requirements set by the USP. 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 14.0 min 0 500 1000 1500 2000 2500 3000 3500 4000 uV PG (b) 2,2,2-trichloroethanol (IS) ED and DEG peak is not detected 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0 min 0 500 1000 1500 2000 2500 3000 3500 4000 uV 2,2,2-trichloroethanol (IS) Glycerin (a) ED and DEG peak is not detected 1.00 1.25 1.50 1.75 2.00 2.25 2.50 2.75 3.00 3.25 min 0 5000 10000 15000 20000 25000 30000 35000 40000 uV (c) EG Impurity peak from acetone DEG peak is not detected Figure 5. Overlay of standard (blue) and sample (pink) for (a) glycerin and (b) PG peak Glycerin PG Standard Average RT (n=5) /min 14.824 4.872 Sample Average RT (n=3) /min 15.052 4.931 Table 6. Retention time of glycerin and PG in standard and sample Analysis of Sample Glycerin Sample and PG Sample Figure 4a-b shows the chromatograms of raw material samples, i.e. glycerin and PG. Table 6 summarizes the average RT of peaks of interest during the analysis, for its standard and sample. Comparison between the standard and sample during the analysis for glycerin raw material, a slight shift in RT of around 0.228 min was observed (Table 6). This was mainly due to the difference in the amount of glycerin that was originally present in both the standard and sample. As depicted in Figure 5a, glycerin’s peak area was much larger in the sample as compared to the standard, this resulted in the shift in the apex of the peak, which is detected as RT. However, the shift is very slight and does not pose any difficulty during peak identification. This effect is also observed in PG (Figure 5b) but to a lesser degree. Thus, for PG, the shift in peak is much less. Hence glycerin and PG peaks were successfully identified in the sample, and their observed RTs were similar to their respective standards. In summary, the USP requirement for the acceptance criteria that requires the RT of glycerin and PG in the sample to be in strong agreement with the standard is successfully achieved in this experiment. EG and DEG peaks were not detected in these analyses. Thus, these 2 raw materials samples cleared the requirement set by USP. 14.0 15.0 min 0 250000 500000 750000 1000000 1250000 1500000 1750000 uV 4.0 5.0 min 0 1000000 2000000 3000000 4000000 5000000 uV (a) (b)
Application News Spiked Sample Glycerin Spiked Sample PG Spiked Sample Sorbitol Spiked Sample Injection Peak Response Ratio (EG/IS # ) Peak Response Ratio (DEG/IS # ) Peak Response Ratio (EG/IS # ) Peak Response Ratio (DEG/IS # ) Peak Area (EG) Peak Area (DEG) 1 0.984 0.869 0.989 0.819 56,281 59,366 2 0.974 0.879 1.026 0.848 55,736 58,958 3 0.992 0.898 1.000 0.815 56,180 59,422 Average 0.983 0.882 1.005 0.827 56,066 59,249 Standard Average 0.893* 0.788* 0.854* 0.725* 44,361* 45,154* Table 8. Summarized result of EG and DEG detected in glycerin, PG and sorbitol spiked samples *These results obtained from Table 5. # Denotes Internal Standard. Figure 6. Chromatograms of (a) glycerin spiked sample, (b) PG spiked sample and (c) sorbitol spiked sample 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0 min 0 500 1000 1500 2000 2500 3000 3500 4000 4500 uV EG 2,2,2-trichloroethanol (IS) DEG (a) Glycerin 1.00 1.25 1.50 1.75 2.00 2.25 2.50 2.75 3.00 3.25 min 0 5000 10000 15000 20000 25000 30000 35000 40000 45000 50000 uV (c) EG DEG Impurity peak from acetone EG PG (b) 2,2,2-trichloroethanol (IS) DEG 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 14.0 min 0 500 1000 1500 2000 2500 3000 3500 4000 4500 uV Test Sample Sorbitol Sample Injection Peak Area (EG) 1 2,293 2 2,063 3 2,101 Average 2,153 Sorbitol Standard Sample’s Average Peak Area 44,361* Table 7. Summarized results of EG detected in sorbitol sample *This result obtained from Table 5 Analysis of Spiked Samples To validate the method, we simulated samples that exceed the acceptance criteria set by USP monographs. All raw material samples were spiked with 0.11% of USP EG and USP DEG each, a slightly higher amount than the specified limit (0.10%). These spiked samples were then analyzed using the same USP method described in Table 1. Figure 6 a-c presents the chromatograms of the spiked samples for glycerin, PG and sorbitol, respectively. Table 8 summarizes EG and DEG’s peak response ratios or peak areas across all spiked samples. The results clearly indicate that the peak response ratios of EG/IS and DEG/IS in the glycerin and PG spiked samples surpass the average peak response ratios
Application News Copyright © 2023 Shimadzu Corporation and/or its affiliates. All rights reserved. For Research Use Only. Not for use in diagnostic procedures. This publication may contain references to products that are not available in your country. Please contact us to check the availability of these products in your country. The content of this publication shall not be reproduced, altered or sold for any commercial purpose without the written approval of Shimadzu. See http://www.shimadzu.com/about/trademarks/index.html for details. Third party trademarks and trade names may be used in this publication to refer to either the entities or their products/services, whether or not they are used with trademark symbol “TM” or “”. The information contained herein is provided to you "as is" without warranty of any kind including without limitation warranties as to its accuracy or completeness. Shimadzu does not assume any responsibility or liability for any damage, whether direct or indirect, relating to the use of this publication. This publication is based upon the information available to Shimadzu on or before the date of publication, and subject to change without notice. Shimadzu Corporation www.shimadzu.com/an/ SHIMADZU (Asia Pacific) Pte. Ltd, www.shimadzu.com.sg First Edition: Oct 2023 04-AD-0293-EN observed in the standards. Similarly, for the sorbitol spiked sample, the average peak areas of EG and DEG exceeded that of the standard. Calculation The RRT of interest analytes for both the standard and sample in the glycerin and PG are calculated using the formula below: Note: Reference peak refers to the examined substance (glycerin or PG). The peak response ratio of EG and DEG to the 2,2,2- trichloroethanol (IS) for both the standard and sample in the glycerin and PG are calculated using the formulae below: Conclusion The application news successfully demonstrates the capability of Shimadzu’s GC-2010 Pro coupled with the AOC-20i+s Plus autosampler to perform the analysis of EG and DEG in raw materials (glycerin, PG and sorbitol) to be used for the manufacturing of medicinal syrup. The system exhibited remarkable performance, as evidenced by the superior resolution observed among the analytes peak of interests, meeting the SST requirement specified in respective raw materials monographs. Great precision of the analytical results was also obtained, as seen from the low %RSD. Our proposed setup ensures the safety of raw materials used in the pharmaceutical and healthcare industries. References 1. WHO says toxic syrup risk 'ongoing', more countries hit. Channel NewsAsia, https://www.channelnewsasia.com/asia/toxic-cough- syrup-deaths-who-ongoing-risk-more-countries-3567291, [Accessed 28 June 2023] 2. WHO issues alert against Indian cough syrups blamed for Uzbek deaths. The Straits Times, https://www.straitstimes.com/asia/south-asia/who-issues- alert-against-indian-cough-syrups-blamed-for-uzbek- deaths, [Accessed 28 June 2023] 3. Indonesia police probe drug regulators over cough syrup. Channel NewsAsia, https://www.channelnewsasia.com/asia/indonesia-drug- police-probe-cough-syrup-3586426, [Accessed 27 June 2023] 4. Chia, C. G. et al., Screening of Ethylene Glycol and Diethylene Glycol in Medicinal Syrup by GCMS with FASST mode (Part 1 – as per Indonesia BPOM Method), Shimadzu Application News No. 04-AD-0283-EN 5. Chia, C. G. et al., Screening of Ethylene Glycol and Diethylene Glycol in Medicinal Syrup by GCMS with FASST mode (Part 2 – Improved Method for QC Testing), Shimadzu Application News No. 04-AD-0288-EN 6. USP Monographs: Glycerin; Official as of 01-May-2020 https://online.uspnf.com/uspnf/document/1_GUID- 6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US, [Accessed 15 July 2021] 7. USP Monographs: Propylene Glycol; Official as of 01-May- 2020, https://online.uspnf.com/uspnf/document/1_GUID- 689CC49B-D676-4822-9F97-1404FD00CF7C_4_en-US, [Accessed 31 July 2021] 8. USP Monographs: Sorbitol Solution; Official as of 01-May- 2021, https://online.uspnf.com/uspnf/document/1_GUID- 379C543A-4FCE-4A2A-9C11-8BEEDA760718_4_en-US, [Accessed 01 August 2021] 9. USP General Chapter<621>, “Chromatography”. https://doi.org/10.31003/USPNF_M99380_06_01, [Accessed 16 March 2022] Peak Response Ratio for EG = Peak Area EG Peak Area of 2,2,2-trichloroethanol Peak Response Ratio for DEG = Peak Area DEG Peak Area of 2,2,2-trichloroethanol RRT = Retention Time of the Peak of Interest Retention Time of the Reference Peak
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