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Clinica Chimica Acta：超高效液相色谱-串联质谱法测定外周血单核细胞钙调磷酸酶活性

2019-09-22 gladiator MedSci原创

钙调磷酸酶活性
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在移植后常规使用钙调神经磷酸酶抑制剂-他克莫司(TAC)的治疗性药物监测。目前，calcineurin活性的测定已被认为是一种有前景的临床工具，以评估疗效和优化药物剂量。本研究的主要目的是建立一种超高效液相色谱-串联质谱法测定外周血单核细胞磷酸酶钙调磷酸酶活性(CNA)的方法，并按照FDA和EMA指南进行验证。

在移植后常规使用钙调神经磷酸酶抑制剂-他克莫司(TAC)的治疗性药物监测。目前，calcineurin活性的测定已被认为是一种有前景的临床工具，以评估疗效和优化药物剂量。本研究的主要目的是建立一种超高效液相色谱-串联质谱法测定外周血单核细胞磷酸酶钙调磷酸酶活性(CNA)的方法，并按照FDA和EMA指南进行验证。

该方法基于监测磷酸肽底物的Ca2+依赖性脱磷酸化。在5名健康志愿者和5名肾移植患者中，在药物摄入前接受每日两次TAC制剂的CNA评估。此外,我们研究了药效的TAC TAC在不同药物剂量和血药浓度间隔(0、1、3、6和12 h)。

我们的研究结果显示：线性范围在0.04 - -2.00 μM量化的下限为0.04 μM。变异系数<4.3%，绝对相对偏差< 10.3%。肽复苏为91.6 ± 4.0%。基质效应研究显示离子抑制，未见结转和干扰。健康组与接受taco治疗组CNA无显著差异。此外，CAN具有最大抑制药物摄入后1 h TAC达到血药浓度最高。

研究表明，该方法改进了PBMCs的萃取相，与其他方法相比，具有测定速度快的优点，使其更接近于在实验室的日常应用。

原始出处：

Pere Fontova，Raül Rigo-Bonnin，Measurement of calcineurin activity in peripheral blood mononuclear cells by ultra-high performance liquid chromatography-tandem mass spectrometry. Renal transplant recipients application (pharmacodynamic monitoring)

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    2020-09-04 windight

    #CTA#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1849739, encodeId=03f91849e3930, content=<a href='/topic/show?id=61815385aa' target=_blank style='color:#2F92EE;'>#CTA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5385, encryptionId=61815385aa, topicName=CTA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Fri Sep 04 08:35:00 CST 2020, time=2020-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1987083, encodeId=9cde198e08370, content=<a href='/topic/show?id=0c4742822df' target=_blank style='color:#2F92EE;'>#外周血单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42822, encryptionId=0c4742822df, topicName=外周血单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=316c73, createdName=caoliehu, createdTime=Mon Mar 02 16:35:00 CST 2020, time=2020-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1662303, encodeId=6d9a1662303e9, content=<a href='/topic/show?id=6a426545472' target=_blank style='color:#2F92EE;'>#测定#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65454, encryptionId=6a426545472, topicName=测定)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8db925396819, createdName=丁鹏鹏, createdTime=Wed Feb 26 05:35:00 CST 2020, time=2020-02-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1299133, encodeId=17011299133bc, content=<a href='/topic/show?id=2b85362063c' target=_blank style='color:#2F92EE;'>#单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36206, encryptionId=2b85362063c, topicName=单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=daa8281, createdName=雕雕, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553365, encodeId=b717155336504, content=<a href='/topic/show?id=81bd923e559' target=_blank style='color:#2F92EE;'>#质谱#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92375, encryptionId=81bd923e559, topicName=质谱)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96fd14366106, createdName=jeanqiuqiu, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578555, encodeId=c91915e85553d, content=<a href='/topic/show?id=fd724282021' target=_blank style='color:#2F92EE;'>#外周血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42820, encryptionId=fd724282021, topicName=外周血)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a31916414168, createdName=ms3994565386320060, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1596044, encodeId=e323159604450, content=<a href='/topic/show?id=7b24e386455' target=_blank style='color:#2F92EE;'>#磷酸酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73864, encryptionId=7b24e386455, topicName=磷酸酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=584e18318123, createdName=andy2093, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=)]
    2020-03-02 caoliehu

    #外周血单核细胞#

    0

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    2020-02-26 丁鹏鹏

    #测定#

    0

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    2019-09-24 雕雕

    #单核细胞#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1849739, encodeId=03f91849e3930, content=<a href='/topic/show?id=61815385aa' target=_blank style='color:#2F92EE;'>#CTA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5385, encryptionId=61815385aa, topicName=CTA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Fri Sep 04 08:35:00 CST 2020, time=2020-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1987083, encodeId=9cde198e08370, content=<a href='/topic/show?id=0c4742822df' target=_blank style='color:#2F92EE;'>#外周血单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42822, encryptionId=0c4742822df, topicName=外周血单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=316c73, createdName=caoliehu, createdTime=Mon Mar 02 16:35:00 CST 2020, time=2020-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1662303, encodeId=6d9a1662303e9, content=<a href='/topic/show?id=6a426545472' target=_blank style='color:#2F92EE;'>#测定#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65454, encryptionId=6a426545472, topicName=测定)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8db925396819, createdName=丁鹏鹏, createdTime=Wed Feb 26 05:35:00 CST 2020, time=2020-02-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1299133, encodeId=17011299133bc, content=<a href='/topic/show?id=2b85362063c' target=_blank style='color:#2F92EE;'>#单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36206, encryptionId=2b85362063c, topicName=单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=daa8281, createdName=雕雕, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553365, encodeId=b717155336504, content=<a href='/topic/show?id=81bd923e559' target=_blank style='color:#2F92EE;'>#质谱#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92375, encryptionId=81bd923e559, topicName=质谱)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96fd14366106, createdName=jeanqiuqiu, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578555, encodeId=c91915e85553d, content=<a href='/topic/show?id=fd724282021' target=_blank style='color:#2F92EE;'>#外周血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42820, encryptionId=fd724282021, topicName=外周血)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a31916414168, createdName=ms3994565386320060, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1596044, encodeId=e323159604450, content=<a href='/topic/show?id=7b24e386455' target=_blank style='color:#2F92EE;'>#磷酸酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73864, encryptionId=7b24e386455, topicName=磷酸酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=584e18318123, createdName=andy2093, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=)]
    2019-09-24 jeanqiuqiu

    #质谱#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1849739, encodeId=03f91849e3930, content=<a href='/topic/show?id=61815385aa' target=_blank style='color:#2F92EE;'>#CTA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5385, encryptionId=61815385aa, topicName=CTA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Fri Sep 04 08:35:00 CST 2020, time=2020-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1987083, encodeId=9cde198e08370, content=<a href='/topic/show?id=0c4742822df' target=_blank style='color:#2F92EE;'>#外周血单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42822, encryptionId=0c4742822df, topicName=外周血单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=316c73, createdName=caoliehu, createdTime=Mon Mar 02 16:35:00 CST 2020, time=2020-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1662303, encodeId=6d9a1662303e9, content=<a href='/topic/show?id=6a426545472' target=_blank style='color:#2F92EE;'>#测定#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65454, encryptionId=6a426545472, topicName=测定)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8db925396819, createdName=丁鹏鹏, createdTime=Wed Feb 26 05:35:00 CST 2020, time=2020-02-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1299133, encodeId=17011299133bc, content=<a href='/topic/show?id=2b85362063c' target=_blank style='color:#2F92EE;'>#单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36206, encryptionId=2b85362063c, topicName=单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=daa8281, createdName=雕雕, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553365, encodeId=b717155336504, content=<a href='/topic/show?id=81bd923e559' target=_blank style='color:#2F92EE;'>#质谱#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92375, encryptionId=81bd923e559, topicName=质谱)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96fd14366106, createdName=jeanqiuqiu, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578555, encodeId=c91915e85553d, content=<a href='/topic/show?id=fd724282021' target=_blank style='color:#2F92EE;'>#外周血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42820, encryptionId=fd724282021, topicName=外周血)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a31916414168, createdName=ms3994565386320060, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1596044, encodeId=e323159604450, content=<a href='/topic/show?id=7b24e386455' target=_blank style='color:#2F92EE;'>#磷酸酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73864, encryptionId=7b24e386455, topicName=磷酸酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=584e18318123, createdName=andy2093, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=)]
    2019-09-24 ms3994565386320060

    #外周血#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1849739, encodeId=03f91849e3930, content=<a href='/topic/show?id=61815385aa' target=_blank style='color:#2F92EE;'>#CTA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5385, encryptionId=61815385aa, topicName=CTA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Fri Sep 04 08:35:00 CST 2020, time=2020-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1987083, encodeId=9cde198e08370, content=<a href='/topic/show?id=0c4742822df' target=_blank style='color:#2F92EE;'>#外周血单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42822, encryptionId=0c4742822df, topicName=外周血单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=316c73, createdName=caoliehu, createdTime=Mon Mar 02 16:35:00 CST 2020, time=2020-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1662303, encodeId=6d9a1662303e9, content=<a href='/topic/show?id=6a426545472' target=_blank style='color:#2F92EE;'>#测定#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65454, encryptionId=6a426545472, topicName=测定)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8db925396819, createdName=丁鹏鹏, createdTime=Wed Feb 26 05:35:00 CST 2020, time=2020-02-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1299133, encodeId=17011299133bc, content=<a href='/topic/show?id=2b85362063c' target=_blank style='color:#2F92EE;'>#单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36206, encryptionId=2b85362063c, topicName=单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=daa8281, createdName=雕雕, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553365, encodeId=b717155336504, content=<a href='/topic/show?id=81bd923e559' target=_blank style='color:#2F92EE;'>#质谱#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92375, encryptionId=81bd923e559, topicName=质谱)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96fd14366106, createdName=jeanqiuqiu, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578555, encodeId=c91915e85553d, content=<a href='/topic/show?id=fd724282021' target=_blank style='color:#2F92EE;'>#外周血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42820, encryptionId=fd724282021, topicName=外周血)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a31916414168, createdName=ms3994565386320060, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1596044, encodeId=e323159604450, content=<a href='/topic/show?id=7b24e386455' target=_blank style='color:#2F92EE;'>#磷酸酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73864, encryptionId=7b24e386455, topicName=磷酸酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=584e18318123, createdName=andy2093, createdTime=Tue Sep 24 07:35:00 CST 2019, time=2019-09-24, status=1, ipAttribution=)]
    2019-09-24 andy2093

    #磷酸酶#

    0

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