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Article(id=1228268588746867451, tenantId=1146029695717560320, journalId=1227999776411738115, issueId=1228268587459216114, articleNumber=null, orderNo=null, doi=10.12048/j.issn.1674-229X.2025.08.007, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1724947200000, receivedDateStr=2024-08-30, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1770771651684, onlineDateStr=2026-02-11, pubDate=1756051200000, pubDateStr=2025-08-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1770771651684, onlineIssueDateStr=2026-02-11, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1770771651684, creator=13701087609, updateTime=1770771651684, updator=13701087609, issue=Issue{id=1228268587459216114, tenantId=1146029695717560320, journalId=1227999776411738115, year='2025', volume='35', issue='8', pageStart='561', pageEnd='640', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1770771651377, creator=13701087609, updateTime=1770795163631, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1228367205105075039, tenantId=1146029695717560320, journalId=1227999776411738115, issueId=1228268587459216114, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1228367205105075040, tenantId=1146029695717560320, journalId=1227999776411738115, issueId=1228268587459216114, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=598, endPage=601, ext={EN=ArticleExt(id=1228268588969165571, articleId=1228268588746867451, tenantId=1146029695717560320, journalId=1227999776411738115, language=EN, title=Determination of the Concentrations of 4 Kinds of β-lactam Antibiotics in Human Plasma by HPLC, columnId=null, journalTitle=Pharmacy Today, columnName=null, runingTitle=null, highlight=null, articleAbstract=
OBJECTIVE

To establish a simple and economical high performance liquid chromatography (HPLC) method for determination of the concentrations of ceftazidime, meropenem, ceftriaxone and cefoperazone in human plasma.

METHODS

The analysis was performed using an Agilent Extend C18 (4.6 mm × 250 mm, 5 μm) chromatographic column, and protein components were removed using ultrafiltration tubes. A gradient elution system consisting of acetonitrile and 50 mmol·L-1 sodium dihydrogen phosphate (pH 2.4) was employed as the mobile phase. The column temperature was maintained at 35 °C, with a flow rate of 1 mL·min-1. Detection was achieved using a dual-wavelength ultraviolet spectrophotometry at 250 and 300 nm.

RESULTS

The four β-lactam antibiotics exhibited good linearity within their respective ranges (r2> 0.999), with an average extraction recovery ranging from 68.98% to 83.50%. The intra-day precision RSD was between 0.06% and 2.67%, while the inter-day precision RSD was between 0.04% and 3.32%.

CONCLUSION

This study successfully established an HPLC method for the determination of the concentrations of ceftazidime, meropenem, ceftriaxone, and cefoperazone, which is suitable for monitoring the plasma concentrations of these four β-lactam antibiotics.

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目的

建立简单经济的高效液相色谱法（HPLC），用于检测人血浆中头孢他啶、美罗培南、头孢曲松和头孢哌酮4种β-内酰胺类抗生素浓度。

方法

采用Agilent Extend C18（4.6 mm × 250 mm，5 μm）色谱柱，使用超滤管去除蛋白成分。乙腈、50 mmol·L-1磷酸二氢钠（pH 2.4）作为流动相梯度洗脱，柱温35 ℃，流速1 mL·min-1，采用250、300 nm双波长紫外分光光度法检测。

结果

4种β-内酰胺类抗生素在各自范围内线性关系良好（r2>0.999），平均提取回收率68.98%～83.5%，日内精密度RSD 0.06%～2.67%，日间精密度RSD 0.04% ~3.32%。

结论

本研究成功建立头孢他啶、美罗培南、头孢曲松和头孢哌酮的HPLC方法，适用用于这4种β-内酰胺类抗生素的血药浓度监测。

, correspAuthors=熊锋, authorNote=null, correspAuthorsNote=
* 熊锋，本科，主任药师，从事临床药学，E-mail：
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陈文露，硕士，主管药师，从事药理学研究和药事管理，E-mail：

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陈文露，硕士，主管药师，从事药理学研究和药事管理，E-mail：

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陈文露，硕士，主管药师，从事药理学研究和药事管理，E-mail：

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Improving antibiotic dosing in special situations in the ICU: burns, renal replace ment therapy and extracorporeal membrane oxygenation[J]. Curr Opin Crit Care, 2012, 18(6): 460-471., articleTitle=Improving antibiotic dosing in special situations in the ICU: burns, renal replace ment therapy and extracorporeal membrane oxygenation, refAbstract=null), Reference(id=1228268597840117777, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, doi=null, pmid=null, pmcid=null, year=2015, volume=46, issue=4, pageStart=367, pageEnd=375, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=Carlier M, Stove V, Wallis S, journalName=Int J Antimicrob Agents, refType=null, unstructuredReference=Carlier M, Stove V, Wallis S, et al. Assays for therapeutic drug monitoring of β-lactam antibiotics: a structured review[J]. Int J Antimicrob Agents, 2015, 46(4): 367-375., articleTitle=Assays for therapeutic drug monitoring of β-lactam antibiotics: a structured review, refAbstract=null), Reference(id=1228268598016278547, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, doi=null, pmid=null, pmcid=null, year=2023, volume=40, issue=22, pageStart=3158, pageEnd=3163, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=陈灵, 郭婷, 邵钰, journalName=中国现代应用药学, refType=null, unstructuredReference=陈灵, 郭婷, 邵钰, 等. 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HPLC法测定人血浆中美罗培南与亚胺培南的浓度[J]. 海峡药学, 2022, 34(7): 87-90., articleTitle=HPLC法测定人血浆中美罗培南与亚胺培南的浓度, refAbstract=null), Reference(id=1228268598364405782, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, doi=null, pmid=null, pmcid=null, year=2012, volume=null, issue=907, pageStart=178, pageEnd=184, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=Scott E, Brett C, Jeffrey L, journalName=J Chromatogr B, refType=null, unstructuredReference=Scott E, Brett C, Jeffrey L, et al. A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection[J]. J Chromatogr B, 2012(907): 178-184., articleTitle=A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection, refAbstract=null), Reference(id=1228268598511206424, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, doi=null, pmid=null, pmcid=null, year=2017, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=蒋琪, journalName=null, refType=null, unstructuredReference=蒋琪. 枫蓼颗粒剂的制备工艺、质量标准及药效学研究[D]. 广州: 广东药科大学, 2017., articleTitle=枫蓼颗粒剂的制备工艺、质量标准及药效学研究, refAbstract=null)], funds=[Fund(id=1228268596741211126, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, awardId=2023A23, language=CN, fundingSource=广东省医院药学研究基金(2023A23), fundOrder=null, country=null), Fund(id=1228268596862845946, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, awardId=2022CZ010371, language=CN, fundingSource=惠州市科技计划项目(2022CZ010371), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1228268590160347962, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, xref=null, ext=[AuthorCompanyExt(id=1228268590168736570, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, companyId=1228268590160347962, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Pharmacy Department of Huidong Hospital, Huizhou, Guangdong 516300, China), AuthorCompanyExt(id=1228268590172930875, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, companyId=1228268590160347962, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=惠东县人民医院药剂科，广东　惠州　516300)])], figs=[ArticleFig(id=1228268594157519822, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=EN, label=null, caption=null, figureFileSmall=+MKOQ582DkhCXTpfkl2dRw==, figureFileBig=y5opsBUs8XyG6NYeCF2B0g==, tableContent=null), ArticleFig(id=1228268594262377428, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=CN, label=图1, caption=各成分HPLC色谱图

注：1.头孢曲松；2.美罗培南；3.头孢他啶；4.头孢哌酮。A.对照品溶液250 nm；B.对照品溶液300 nm；C.空白血浆样品250 nm；D.空白血浆样品300 nm；E.血浆对照品250 nm；F.血浆对照品300 nm。

, figureFileSmall=+MKOQ582DkhCXTpfkl2dRw==, figureFileBig=y5opsBUs8XyG6NYeCF2B0g==, tableContent=null), ArticleFig(id=1228268594463704026, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
时间/min乙腈/%50 mmol·L-1磷酸二氢钠（pH2.4）/%
0892
31288
113070
15892
), ArticleFig(id=1228268594555978717, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=CN, label=表1, caption=

梯度洗脱程序

, figureFileSmall=null, figureFileBig=null, tableContent=
时间/min乙腈/%50 mmol·L-1磷酸二氢钠（pH2.4）/%
0892
31288
113070
15892
), ArticleFig(id=1228268594627281890, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
成分回归方程r2线性范围/μg检测限/μg
美罗培南Y=12.947X-38.620.999 31~4001
头孢他啶Y=20.122X+42.3050.999 01~4001
头孢哌酮Y=5.679 6X+0.705 90.999 12.5~2002.5
头孢曲松Y=18.356X-20.0750.999 21~4001
), ArticleFig(id=1228268594719556580, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=CN, label=表2, caption=

4种抗生素线性关系及检测限

, figureFileSmall=null, figureFileBig=null, tableContent=
成分回归方程r2线性范围/μg检测限/μg
美罗培南Y=12.947X-38.620.999 31~4001
头孢他啶Y=20.122X+42.3050.999 01~4001
头孢哌酮Y=5.679 6X+0.705 90.999 12.5~2002.5
头孢曲松Y=18.356X-20.0750.999 21~4001
), ArticleFig(id=1228268594862162919, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
药品名称浓度/μg·mL-1日内RSD/%日间RSD/%
2000.390.04
美罗培南1000.211.61
250.180.83
2000.150.04
头孢曲松1000.061.52
250.320.32
2002.671.75
头孢他啶1002.280.54
252.100.43
2000.230.11
头孢哌酮1000.353.32
250.492.07
), ArticleFig(id=1228268594987992040, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=CN, label=表3, caption=

4种抗生素精密度

, figureFileSmall=null, figureFileBig=null, tableContent=
药品名称浓度/μg·mL-1日内RSD/%日间RSD/%
2000.390.04
美罗培南1000.211.61
250.180.83
2000.150.04
头孢曲松1000.061.52
250.320.32
2002.671.75
头孢他啶1002.280.54
252.100.43
2000.230.11
头孢哌酮1000.353.32
250.492.07
), ArticleFig(id=1228268596414055404, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
药品名称浓度/μg·mL-1提取回收率（n=5）/%RSD/%
美罗培南25072.59±0.921.56
12572.75±0.831.39
12.569.97±1.512.64
头孢曲松25083.28±0.971.42
12583.50±1.181.73
12.577.81±1.141.79
头孢他啶25072.24±1.182.01
12574.72±0.871.43
12.573.07±1.472.47
头孢哌酮25073.99±1.232.04
12568.98±1.432.54
12.570.39±1.252.17
), ArticleFig(id=1228268596544078833, tenantId=1146029695717560320, journalId=1227999776411738115, articleId=1228268588746867451, language=CN, label=表4, caption=

4种抗生素提取回收率（）

, figureFileSmall=null, figureFileBig=null, tableContent=
药品名称浓度/μg·mL-1提取回收率（n=5）/%RSD/%
美罗培南25072.59±0.921.56
12572.75±0.831.39
12.569.97±1.512.64
头孢曲松25083.28±0.971.42
12583.50±1.181.73
12.577.81±1.141.79
头孢他啶25072.24±1.182.01
12574.72±0.871.43
12.573.07±1.472.47
头孢哌酮25073.99±1.232.04
12568.98±1.432.54
12.570.39±1.252.17
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HPLC法测定人血浆中4种β-内酰胺类抗生素浓度
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陈文露 , 熊锋 * , 赖剑峰 , 刘惠霞 , 魏洁 , 廖晗 , 刘菊媚
今日药学 | 论著 2025,35(8): 598-601
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今日药学 | 论著 2025, 35(8): 598-601
HPLC法测定人血浆中4种β-内酰胺类抗生素浓度
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陈文露 , 熊锋* , 赖剑峰, 刘惠霞, 魏洁, 廖晗, 刘菊媚
作者信息
  • 惠东县人民医院药剂科，广东　惠州　516300

    • 陈文露，硕士，主管药师，从事药理学研究和药事管理，E-mail：

通讯作者:

* 熊锋，本科，主任药师，从事临床药学，E-mail：
Determination of the Concentrations of 4 Kinds of β-lactam Antibiotics in Human Plasma by HPLC
Wenlu CHEN , Feng XIONG* , Jianfeng LAI, Huixia LIU, Jie WEI, Han LIAO, Jumei LIU
Affiliations
  • Pharmacy Department of Huidong Hospital, Huizhou, Guangdong 516300, China
出版时间: 2025-08-25 doi: 10.12048/j.issn.1674-229X.2025.08.007
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摘要
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目的

建立简单经济的高效液相色谱法（HPLC），用于检测人血浆中头孢他啶、美罗培南、头孢曲松和头孢哌酮4种β-内酰胺类抗生素浓度。

方法

采用Agilent Extend C18（4.6 mm × 250 mm，5 μm）色谱柱，使用超滤管去除蛋白成分。乙腈、50 mmol·L-1磷酸二氢钠（pH 2.4）作为流动相梯度洗脱，柱温35 ℃，流速1 mL·min-1，采用250、300 nm双波长紫外分光光度法检测。

结果

4种β-内酰胺类抗生素在各自范围内线性关系良好（r2>0.999），平均提取回收率68.98%～83.5%，日内精密度RSD 0.06%～2.67%，日间精密度RSD 0.04% ~3.32%。

结论

本研究成功建立头孢他啶、美罗培南、头孢曲松和头孢哌酮的HPLC方法，适用用于这4种β-内酰胺类抗生素的血药浓度监测。

高效液相色谱法  /  β-内酰胺类抗生素  /  血药浓度
OBJECTIVE

To establish a simple and economical high performance liquid chromatography (HPLC) method for determination of the concentrations of ceftazidime, meropenem, ceftriaxone and cefoperazone in human plasma.

METHODS

The analysis was performed using an Agilent Extend C18 (4.6 mm × 250 mm, 5 μm) chromatographic column, and protein components were removed using ultrafiltration tubes. A gradient elution system consisting of acetonitrile and 50 mmol·L-1 sodium dihydrogen phosphate (pH 2.4) was employed as the mobile phase. The column temperature was maintained at 35 °C, with a flow rate of 1 mL·min-1. Detection was achieved using a dual-wavelength ultraviolet spectrophotometry at 250 and 300 nm.

RESULTS

The four β-lactam antibiotics exhibited good linearity within their respective ranges (r2> 0.999), with an average extraction recovery ranging from 68.98% to 83.50%. The intra-day precision RSD was between 0.06% and 2.67%, while the inter-day precision RSD was between 0.04% and 3.32%.

CONCLUSION

This study successfully established an HPLC method for the determination of the concentrations of ceftazidime, meropenem, ceftriaxone, and cefoperazone, which is suitable for monitoring the plasma concentrations of these four β-lactam antibiotics.

HPLC  /  β-lactam antibiotics  /  plasma concentration
陈文露, 熊锋, 赖剑峰, 刘惠霞, 魏洁, 廖晗, 刘菊媚. HPLC法测定人血浆中4种β-内酰胺类抗生素浓度. 今日药学, 2025 , 35 (8) : 598 -601 . DOI: 10.12048/j.issn.1674-229X.2025.08.007
Wenlu CHEN, Feng XIONG, Jianfeng LAI, Huixia LIU, Jie WEI, Han LIAO, Jumei LIU. Determination of the Concentrations of 4 Kinds of β-lactam Antibiotics in Human Plasma by HPLC[J]. Pharmacy Today, 2025 , 35 (8) : 598 -601 . DOI: 10.12048/j.issn.1674-229X.2025.08.007
正文
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β-内酰胺类抗菌药物是目前临床应用最多且具有重要临床价值的一类抗菌药物[1]，其包括青霉素类、碳青霉烯类和头孢菌素类等。当β -内酰胺类抗生素的浓度为MIC的3~4倍时，对敏感菌产生最大的杀灭效果，而浓度越高，几乎没有额外的细菌杀灭效果[2]。当β-内酰胺类抗生素在感染部位的游离浓度高于目标病原体的MIC（fT>MIC）的时间越长，其杀菌效果越有效[3,4]。
因为β-内酰胺类抗菌药物没有狭窄的治疗窗，所以鲜少有研究报道关于β-内酰胺类抗菌药物的血药浓度监测，医生大多根据说明书和专家指南对患者进行经验性用药，对于一些特殊治疗的患者如连续性肾替代治疗的患者最近有专家组也提出了相关共识[5]，但其对于一些β-内酰胺类抗生素也提出建议进行血药浓度检测，如头孢哌酮。鉴于对β-内酰胺的获得性耐药增加及其与低抗生素血清浓度的关联，对于病情复杂的重症感染患者，进行β-内酰胺类血药浓度监测可能具有更大的临床获益性[6,7]。
本研究采用超滤管高速离心处理血浆样品，简化样品提取过程，建立一种高效液相色谱法可测检4种β-内酰胺类抗生素的血药浓度，避免流动相的浪费，使检测过程更加快捷、简便，为临床β-内酰胺类抗生素治疗血药浓度监测提供参考。
1　材料与方法
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1.1　仪器
Agilent超高液相色谱仪（配置Agilent1260 Infinity Ⅱ样品瓶进样器、Agilent 1260 Infinity Ⅱ全能泵、Agilent 1260 Infinity Ⅱ可变波长检测器），美国Agilent公司；HH-4数显恒温水浴锅，常州澳华仪器有限公司；艾科浦ATR-05-M超纯水系统，重庆颐洋发展有限公司；XS型电子天平（十万分之一），瑞士梅特勒-托利多公司；Eppendorf centrifuge 5418常温台式离心机，德国艾本德股份公司。
1.2　试剂与药物
头孢哌酮（批号：ML230111-04，100%）、头孢他啶（批号：ZJ221126-04，98.2%）、头孢曲松（批号：T220508-12，99.9%）、美罗培南（批号：AP230512-20，99.3%）对照品均购自北方伟业计量集团有限公司；磷酸二氢钠（批号：2020年12月7日，99.0%），购于天津市化工三厂有限公司；乙腈（色谱纯，BCR International Trading）；水为超纯水。
1.3　溶液配置
1.3.1　血浆样品的处理
取血浆样品400 μL，加入至超滤管，12 000 r·min-1，离心10 min，取上清液进样分析。
1.3.2　标准品制备
分别精密称取美罗培南、头孢他啶、头孢曲松和头孢哌酮0.009 98、0.010 04、0.009 91、0.004 96 g用去离子水溶解于10 mL容量瓶并定容得到质量浓度分别为1、1、1、0.5 mg·mL-1的贮备液。精密量吸取适量分别置于5 mL容量瓶并定容，获得美罗培南、头孢他啶、头孢曲松质量浓度分别为1、5、50、200、400 μg·mL-1，头孢哌酮质量浓度分别为2.5、5、25、100、200 μg·mL-1的溶液Ⅰ～Ⅴ，即得。
1.4　色谱条件
采用Agilent Extend C18色谱柱（4.6 mm ×250 mm，5 μm），进样量10 μL，柱温35 ℃，流速1 mL·min-1，双波长250、300 nm，梯度洗脱，程序见表1。
2　方法学确证
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2.1　方法的专属性
在本试验建立的HPLC色谱条件下，头孢曲松的保留时间是5.7 min，美罗培南的保留时间是6.4 min，头孢他啶的保留时间是7.7 min，头孢哌酮的保留时间是12.1 min。典型色谱图见图1，可见血浆样品色谱峰对美罗培南、头孢他啶、头孢曲松和头孢哌酮标准品形无干扰，无前沿峰、拖尾峰，且分离良好。
2.2　标准曲线和定量下限
取对照品溶液适量，在“1.4”项色谱条件下进样测定。以对照品峰面积为纵坐标（Y），质量浓度为横坐标（X）进行回归，各成分在各自范围内线性关系良好，结果见表2。
2.3　精密度
精密度和准确度制备3个浓度质量控制样品各5份，随行标准曲线，按“1.4”项下操作，连续测定3批，记录色谱峰，计算日内和日间精密度RSD，结果见表3。
2.4　回收率
取血浆200 μL，加入美罗培南、头孢他啶、头孢曲松和头孢哌酮50、500、1 000 μg·mL-1系列标准液各50 μL，得12.5、25、250 μg·mL-1，旋涡混匀，3个浓度各5份，按照“1.4”项下方法进样检测，得各峰面积，分别求平均值（记作A1）；抗生素质量控制样品，加入200 μL超纯水，加入美罗培南、头孢他啶、头孢曲松和头孢哌酮50、500、1 000 μg·mL-1系列标准液各50 μL，得12.5、125、250 μg·mL-1；旋涡混匀，3个浓度各5份，直接进样，得各抗生素峰面积，分别求平均值（记作A2）；按以下公式分别计算取美罗培南、头孢他啶、头孢曲松和头孢哌酮的提取回收率，具体结果见表4。
2.5　血浆稳定性考察
配制美罗培南、头孢他啶、头孢曲松和头孢哌酮低、中、高浓度为12.5、125、250 μg·mL-1的血清质控样品各5份，在连续冻融3次，室温下至少稳定6 h，在4 ℃条件下至少稳定24 h，在-20 ℃条件下至少稳定72 h，RSD均在15%之内。
3　讨论
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β-内酰胺类抗生素抗菌谱广、毒性低、治疗窗宽，广泛用于临床抗感染治疗，普遍认为安全性高，但近年来不良反应报道屡见不鲜[8,9]。对于一些特殊患者如重症感染患者、需要连续性肾替代治疗和肾透析的患者等，由于患者病理生理状态的复杂性，药代动力学（PK）和药效学（PD）发生改变，医药工作者难以根据指南、说明书中健康志愿者或轻症患者的PK/PD参数预测患者的治疗效果，更容易出现药物不良反应和剂量不足等情况，对原发疾病治疗的影响不可估量。进行治疗药物监测是优化特殊患者抗生素治疗方案的重要手段，但是目前对于这类抗生素的检测及指导用药并不成熟。尽管有方法已经被用于临床的检测[10]，但总有复杂的前处理步骤或较长的测定时间等不便之处。
本研究初期对样品处理方法参考文献[11-14]处理比较后发现，直接用超滤管处理血浆样品可较为彻底的去除蛋白，并提高检测限，降低杂质干扰。对磷酸缓冲盐如磷酸二氢钾[11]、磷酸二氢钠[15]进行了浓度和pH的考察，同时考察了有机相乙腈和甲醇，色谱柱Agilent Extend C18色谱柱（4.6 mm × 250 mm，5 μm）和Waters Symmetry shield RP18色谱柱（4.6 mm×250 mm，5.0 μm）[16]。最终确定流动相为50 mmol·L-1磷酸二氢钠（pH2.4）和乙腈进行梯度洗脱，在此色谱条件下美罗培南、头孢他啶、头孢曲松和头孢哌酮的分离度较好、峰型良好、保留时间适中，整体洗脱时间可控制在15 min。
此方法血浆样品处理方便，检测过程快捷方便，与质谱检测或较新的超高性能液相色谱系统相比，分析仪器相对普遍；检测费用和液相质谱相比较为经济。能够使用一个简单而廉价的检测手段分析β-内酰胺类抗生素在病人血液中的药物浓度，对于降低细菌耐药率、使用合理的抗生素药物浓度和提高患者的就医体验是非常的有必要的。
综上所述，本研究建立的头孢他啶、美罗培南、头孢曲松和头孢哌酮HPLC方法，为临床合理应用这4种β-内酰胺类抗生素提供了一个有力工具。
基金
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  • 广东省医院药学研究基金(2023A23)
  • 惠州市科技计划项目(2022CZ010371)
文献
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参考文献 引证文献
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2025年第35卷第8期
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doi: 10.12048/j.issn.1674-229X.2025.08.007
  • 接收时间：2024-08-30
  • 首发时间：2026-02-11
  • 出版时间：2025-08-25
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  • 收稿日期：2024-08-30
基金
广东省医院药学研究基金(2023A23)
惠州市科技计划项目(2022CZ010371)
作者信息
    惠东县人民医院药剂科，广东　惠州　516300

通讯作者:

* 熊锋，本科，主任药师，从事临床药学，E-mail：
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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