离子色谱法同时测定硫酸氢氯吡格雷中甲酸残留及硫酸盐含量

冯顺卿; 卓文珊; 王潇洋; 刘洪涛

doi:10.16495/j.1006-3757.2023.02.007

离子色谱法同时测定硫酸氢氯吡格雷中甲酸残留及硫酸盐含量

doi: 10.16495/j.1006-3757.2023.02.007

中山大学测试中心，广东广州　510275

详细信息

作者简介:
冯顺卿（1978−），女，实验师，主要研究方向：仪器分析，E-mail：ncsfshq@mail.sysu.edu.cn

通讯作者:
刘洪涛（1976−），女，正高级实验师，主要研究方向：分析化学，E-mail：liuht@mail.sysu.edu.cn

中图分类号: O657. 7
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- 文章访问数: 57
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- 被引次数: 0
出版历程
- 收稿日期: 2023-02-01
- 录用日期: 2023-04-13
- 修回日期: 2023-04-13
- 刊出日期: 2023-06-30

Simultaneous Determination of Residual Formic Acid and Content of Sulfate in Clopidogrel Bisulfate by Ion Chromatography

Instrumental Analysis & Research Center, Sun Yat-sen University, Guangzhou 510275, China

摘要

摘要: 建立了离子色谱同时测定硫酸氢氯吡格雷原料药中的甲酸残留及硫酸盐含量的方法. 硫酸氢氯吡格雷原料药以2 mmol/L NaOH水溶液超声提取，经过滤后进样分析. 采用Dionex IonPac AS11-HC（4 mm×250 mm）分析柱以及Dionex IonPac AG11-HC（4 mm×50 mm）保护柱，EG 500 KOH在线产生KOH，梯度洗脱，流速1.3 mL/min，柱温30 ℃，进样体积25 μL，抑制电流90 mA. 结果表明，HCOO⁻在0.020 0~1.00 mg/L范围内、SO₄²⁻在10.0~40.0 mg/L范围内线性关系良好. HCOO⁻、SO₄²⁻检出限分别为10.0、50.0 μg/L，定量限分别为20.0、100 μg/L. 方法前处理简单，灵敏度高，重复性好，适用于硫酸氢氯吡格雷原料药中甲酸残留及硫酸盐含量的同时测定.
- 离子色谱 /
- 硫酸氢氯吡格雷 /
- 甲酸 /
- 硫酸盐
Abstract: A method for the simultaneous determination of residual formic acid and the content of sulfate (SO₄²⁻) in clopidogrel bisulfate active pharmaceutical ingredient (API) by ion chromatography (IC) was developed. Clopidogrel bisulfate API was sonicated by 2 mmol/L NaOH aqueous solution and then filtered. The analysis was performed on a Dionex IonPac AS11-HC analytical column (4 mm×250 mm) in combination with a Dionex IonPac AG11-HC guard column (4 mm×50 mm). The eluent was KOH produced on-line with an EG 500 KOH in the gradient mode at a flow rate of 1.3 mL/min. The column temperature was kept at 30 ℃ and the injection volume was 25 μL. The suppressor current was 90 mA. The test results showed that good linearity existed over the range of 0.020 0~1.00 mg/L for formic acid, and 10.0~40.0 mg/L for sulfate, respectively. The detection limits (LODs) of formic acid and sulfate were 10.0, 50.0 μg/L, respectively, and the quantification limits (LOQs) were 20.0, 100 μg/L, respectively. The method is simple, highly sensitive, and reproducible, and could be suitable for the detection of residual formic acid and the content of sulfate in clopidogrel bisulfate API.
- IC /
- clopidogrel bisulfate /
- formic acid /
- sulfate

HTML全文

图 1 HCOO⁻、SO₄²⁻与易干扰离子（F⁻、CH₃COO⁻、Cl⁻、Br⁻、NO₃⁻、CO₃²⁻、Oxalate、PO₄³⁻）的离子色谱图

Figure 1. Chromatogram of HCOO⁻, SO₄²⁻, and interference ions (F⁻，CH₃COO⁻，Cl⁻、Br⁻，NO₃⁻，CO₃²⁻， Oxalate and PO₄³⁻)

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图 2 （a）2 mmol/L，（b）30 mmol/L NaOH制备的样品溶液添加0.2 mg/L甲酸的色谱图

Figure 2. Chromatograms of sample solution added 0.2 mg/L formic acid in (a) 2 mmol/L NaOH and (b) 30 mmol/L NaOH

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图 3 （a）空白溶液、（b）硫酸氢氯吡格雷样品及（c）0.02 mg/L甲酸对照品溶液的色谱图

Figure 3. Chromatograms of (a) blank, (b) clopidogrel bisulfate and (c) 0.02 mg/L formic acid

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图 4 （a）空白、（b）硫酸氢氯吡格雷样品及（c）0.8 mg/L甲酸对照品的色谱图

Figure 4. Chromatograms of (a) blank, (b) clopidogrel bisulfate and (c) 0.8 mg/L formic acid

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表 1 方法的线性关系、检出限及定量限

Table 1. Linear relationship, limits of detection and limits of quantification

分析物	线性范围/（mg/L）	回归方程	相关系数	检出限/（μg/L）	定量限/（μg/L）
HCOO⁻	0.020 0~1.00	y=0.143 6x+0.002 9	0.998 86	10.0	20.0
SO₄²⁻	10.0~40.0	y=0.177 7x−0.036 9	0.999 99	50.0	100

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表 2 硫酸氢氯吡格雷中甲酸和硫酸盐的加标回收率（n=3）

Table 2. Recoveries of formic acid and sulfate in clopidogrel bisulfate (n=3)

分析物	称样质量/mg	本底质量浓度/ （mg/L）	加标质量浓度/ （mg/L）	加标后质量浓度/ （mg/L）	回收率/%	平均回收率/%	RSD/%
HCOO⁻	6.344	< 0.02	0.100	0.103	103.0	102.0	3.9
	6.684	< 0.02		0.097 8	97.8
	6.634	< 0.02		0.106	106.0
	6.713	< 0.02	0.200	0.185	91.2	93.6	4.4
	6.644	< 0.02		0.185	91.2
	6.541	< 0.02		0.207	98.4
	6.315	< 0.02	0.300	0.274	91.3	92.4	4.2
	6.691	< 0.02		0.290	96.7
	6.696	< 0.02		0.228	89.2
SO₄²⁻	6.315	14.4	12.0	26.6	101.0	101.0	0.8
	6.691	15.3		27.3	101.0
	6.696	15.3		27.2	99.6
	6.344	14.5	15.0	29.7	102.0	100.0	1.5
	6.684	15.2		30.0	98.5
	6.634	15.1		30.1	100.0
	6.713	15.3	18.0	33.3	100.0	101.0	1.1
	6.644	15.1		33.5	102.0
	6.541	14.9		33.2	102.0

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参考文献(17)

[1]	陈旭, 谢荟茹, 张勇, 等. 硫酸氢氯吡格雷片的餐后人体生物等效性研究[J]. 华西药学杂志,2016,31(1):75-78 CHEN Xu, XIE Huiru, ZHANG Yong, et al. Postprandial bioequivalence of Clopidogrel hydrogen sulfate tablets in the healthy volunteers[J]. West China Journal of Pharmaceutical Sciences,2016,31 (1):75-78.
[2]	张丽, 翟所迪. 氯吡格雷治疗冠心病合并慢性肾病的系统评价[J]. 中国药学杂志,2010,45(24):1933-1939 ZHANG Li, ZHAI Suodi. Systematic review in clopidogrel therapy coronary heart disease with chronic nephropathy[J]. Chinese Pharmaceutical Journal,2010,45 (24):1933-1939.
[3]	国家药典委员会. 《中华人民共和国药典》(2020年版二部)[M]. 北京: 中国医药科技出版社, 2020: 1609-1611.
[4]	周长朋, 刘敏, 李大栓, 等. 离子色谱-电化学法测定坎地沙坦酯药物中羟胺残留[J]. 分析测试学报,2018,37(6):754-758 ZHOU Changpeng, LIU Min, LI Dashuan, et al. Determination of hydroxylamine residues in candesartan cilexetil drugs by ion chromatography with electrochemical detection[J]. Journal of Instrumental Analysis,2018,37 (6):754-758.
[5]	方琳美, 胡咪, 陈爱连, 等. 离子色谱法测定盐酸阿比朵尔中残留的二甲胺含量[J]. 药物分析杂志,2016,36(10):1852-1856 FANG Linmei, HU Mi, CHEN Ailian, et al. Determination of the residual dimethylamine in arbidol hydrochloride by ion chromatography[J]. Chinese Journal of Pharmaceutical Analysis,2016,36 (10):1852-1856.
[6]	冯顺卿, 李咏华, 李晓燕, 等. 离子色谱法测定酒石酸长春瑞滨中三氟乙酸残留[J]. 药物分析杂志,2013,33(2):289-291 FENG Shunqing, LI Yonghua, LI Xiaoyan, et al. Ion chromatography determination of trifluoroacetic acid residue in vinorelbine tartrate[J]. Chinese Journal of Pharmaceutical Analysis,2013,33 (2):289-291.
[7]	王东武, 刘志娟, 许峰, 等. 氧瓶燃烧-离子色谱电导检测法测定格列喹酮主环物中水合氯醛的含量[J]. 分析测试学报,2015,34(10):1185-1190 doi: 10.3969/j.issn.1004-4957.2015.10.016 WANG Dongwu, LIU Zhijuan, XU Feng, et al. Determination of chloral hydrate in gliquidone main ring by oxygen flask combustion-ion chromatography with electrical conductivity detector[J]. Journal of Instrumental Analysis,2015,34 (10):1185-1190. doi: 10.3969/j.issn.1004-4957.2015.10.016
[8]	粟贵, 刘雁鸣, 龙海燕, 等. 离子色谱法测定药用辅料硬脂酸镁中氯离子和硫酸根离子及不同级别产品含量比较[J]. 药物分析杂志,2016,36(12):2251-2256 SU Gui, LIU Yanming, LONG Haiyan, et al. Determination of chloride ion and sulfate ion in pharmaceutical excipient magnesium stearate by ion chromatography and comparison between different levels of product content[J]. Chinese Journal of Pharmaceutical Analysis,2016,36 (12):2251-2256.
[9]	栾绍嵘, 刘鹏宇, 张芳芳, 等. 磷酸蒸馏-离子色谱法测定药物中的氰根总量[J]. 理化检验-化学分册,2020,56(4):415-418 LUAN Shaorong, LIU Pengyu, ZHANG Fangfang, et al. Determination of total cyanide in drugs by ion chromatography combined with phosphoric acid distillation[J]. Physical Testing and Chemical Analysis (Part B: Chemical Analysis),2020,56 (4):415-418.
[10]	Metil D S, Sampath A, Reddy C V R, et al. Synthesis and characterization of potential related substances of the antiplatelet agent clopidogrel bisulfate[J]. Chemistry Select,2018,3 (1):100-104. doi: 10.1002/slct.201702605
[11]	吕洁, 孟祥军, 王凤秋. 高效液相色谱法测定硫酸氢氯吡格雷中的有关物质[J]. 光谱实验室,2011,28(3):1315-1319 LV Jie, MENG Xiangjun, WANG Fengqiu. Determination of related substances in clopidogrel hydrogen sulfate by HPLC[J]. Chinese Journal of Spectroscopy Laboratory,2011,28 (3):1315-1319.
[12]	美克古丽·艾买提, 艾尔肯·依不拉音. 可调激光-微顺序注射-阀上实验室荧光反猝灭法测定硫酸氢氯吡格雷的含量[J]. 药物分析杂志,2017,37(5):789-795 AMAT Mihray, IBURAYIM Arkin. Quantitative analysis of clopidogrel hydrogen sulfate by fluorescence quenching method in the laboratory of a tunable laser micro sequential injection valve method[J]. Chinese Journal of Pharmaceutical Analysis,2017,37 (5):789-795.
[13]	钱建钦, 张云峰, 王建, 等. UHPLC-MS法测定2种硫酸氢氯吡格雷晶型中的基因毒性杂质对甲苯磺酸甲酯[J]. 药物分析杂志,2017,37(11):1994-1999 QIAN Jianqin, ZHANG Yunfeng, WANG Jian, et al. Determination of genotoxic impurity methyl p-toluenesulfonate in two kinds of crystal forms of clopidogrel hydrogen sulfate[J]. Chinese Journal of Pharmaceutical Analysis,2017,37 (11):1994-1999.
[14]	何佳佳, 黄巧巧, 朱培曦, 等. LC-MS/MS测定硫酸氢氯吡格雷中的痕量四乙基溴化铵[J]. 中国现代应用药学,2017,34(10):1424-1426 HE Jiajia, HUANG Qiaoqiao, ZHU Peixi, et al. Determination of residual tetraethyl ammonium bromide in clopidogrel sulfate by LC-MS/MS[J]. Chinese Journal of Modern Applied Pharmacy,2017,34 (10):1424-1426.
[15]	黄巧巧, 何佳佳, 王宇. 在线基质消除-离子色谱法检测硫酸氢氯吡格雷中四乙基溴化铵的残留[J]. 中国药学杂志,2017,52(19):1727-1730 HUANG Qiaoqiao, HE Jiajia, WANG Yu. On-line matrix elimination-ion chromatography for determination of residual TEAB in clopidogrel sulfate[J]. Chinese Pharmaceutical Journal,2017,52 (19):1727-1730.
[16]	韩学静, 杜增辉, 王熳. 顶空气相色谱法测定硫酸氢氯吡格雷中的有机溶剂残留量[J]. 华西药学杂志,2010,25(5):587-589 HAN Xuejing, DU Zenghui, WANG Man. Determination of residual organic solvents in clopidogrel bisulfate by headspace GC[J]. West China Journal of Pharmaceutical Sciences,2010,25 (5):587-589.
[17]	Pavlović Aleksandar D, Ignjatović Ljubiša M, Popov Saša Z, et al. Application of gas chromatography analysis to quality control of residual organic solvents in clopidogrel bisulphate[J]. Journal of the Serbian Chemical Society,2014,79 (10):1279-1293. doi: 10.2298/JSC131120013P