Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method

The recent and widespread appearance of counterfeit antimalarial tablets in South-east Asia prompted the search for simple field assays to identify genuine drugs. In a recently described colorimetric assay for artesunate, Fast red TR salt reacted with an alkali-decomposition product of artesunate to produce a distinct yellow colour. However, that assay is specific for artesunate and it cannot be used to test for artemether. Because of potential concerns over artemether tablet counterfeiting, the colorimetric assay was modified to detect artemether, dihydroartemisinin and artesunate tablets. Other common antimalarials (artemisinin, chloroquine diphosphate, mefloquine HCl, sulphadoxine and pyrimethamine), as well as aspirin and acetaminophen, were negative in the assay, indicating its specificity for artemether, dihydroartemisinin and artesunate. The colorimetric method can be used to obtain a rapid visual assessment of tablet authenticity. The method can also be used to quantify the drug content of tablets, when used in conjunction with a spectrophotometer.     

Artemisinin-derived antimalarial endoperoxides from bench-side to bed-side: Chronological advancements and future challenges

According to WHO World Malaria Report (2018), nearly 219 million new cases of malaria occurred and a total no. of 435 000 people died in 2017 due to this infectious disease. This is due to the rapid spread of parasite-resistant strains. Artemisinin (ART), a sesquiterpene lactone endoperoxide isolated from traditional Chinese herb Artemisia annua, has been recognized as a novel class of antimalarial drugs. The 2015 “Nobel Prize in Physiology or Medicine” was given to Prof Dr Tu Youyou for the discovery of ART. Hence, ART is termed as “Nobel medicine.” The present review article accommodates insights from the chronological advancements and direct statistics witnessed during the past 48 years (1971-2019) in the medicinal chemistry of ART-derived antimalarial endoperoxides, and their clinical utility in malaria chemotherapy and drug discovery.     

薄层扫描法测定复方蒿甲醚片中蒿甲醚的含量

用薄层色谱法定量扫描技术测定复方蒿甲醚片中的蒿甲醚含量，处方中的本芴醇及杂质无干扰，方法简便，易行，２４～２８ｈ，测定结果稳定，平均回收率为１０１．２％，相对标准偏差为２．３％。     

蒿甲醚、吡喹酮早期治疗感染血吸虫病病兔的肝脏病理变化

兔于感染日本血吸虫尾蚴后ｄ７灌服（ｉｇ）１次蒿甲醚（Ａｒｔ）３０ｍｇ·ｋｇ－１，并于感染后ｄ１４、ｄ２１、ｄ３５和ｄ４９重复ｉｇ１次相同剂量的Ａｒｔ时，在兔肝的切片中仅查见死虫，未见有虫卵或和虫卵性肉芽肿形成。若于感染后ｄ７、ｄ２１、ｄ３５和ｄ４９ｉｇ上述剂量的Ａｒｔ１次时，肝内偶而查见少量虫卵和虫卵性肉芽肿。若于感染后ｄ２１ｉｇ１次吡喹酮（Ｐｒａ）４０ｍｇ·ｋｇ－１，然后每ｗｋ（ｄ２８和ｄ３５）或每２ｗｋ（ｄ３５和ｄ４９）重复ｉｇ１次相同剂量的Ｐｒａ时，前者肝切片查见的虫卵数和虫卵肉芽肿远较对照组的为少，但较后者为多，后者所查见的为陈旧性虫卵或虫卵性芽肿。结果表明兔于感染血吸虫尾蚴后，用Ａｒｔ或Ｐｒａ早期治疗，因大部分或甚至全部♀虫被杀死，肝脏受虫卵损害轻微或无明显损害。     

磷酸萘酚喹、复方蒿甲醚治疗恶性疟的效果

用磷酸萘酚喹总量10片(1000mg)2d分服.复方蒿甲醚16片(含蒿甲醚320mg、苯芴醇1920mg)3d分服各治疗恶性疟25例和21例,两组的临床治愈率均为100％.其平均退热时间、原虫无性体转阴时间分别为47.6h、60.64h和26.3h、33.36h.前者均明显慢于后者(P<0.01).但随访观察至9个月的恶性疟原虫检出率相近(P均>0.05).各为12.0％和9.5％。结果表明,两种药物杀灭清除疟原虫无性体的时间各异,但清除疟原虫的彻底程度则相仿。为克服磷酸萘酚喹作用缓慢和青蒿素类药物疗程显长的不中,建议两药伍用.以期减少剂量、缩短疗程和延缓恶性疟原虫对这两种抗疟新药产生抗之目的。     

蒿甲醚对日本血吸虫核苷摄入和核酸含量的影响

目的： 观察蒿甲醚（ Ａｒｔ） 对日本血吸虫核苷摄入和核酸含量的影响。方法： 感染小鼠１ 次灌服（ｉｇ） Ａｒｔ ３００ ｍｇ／ｋｇ 后２４ ｈ 或４８ ｈ ， 分别测定雌虫（ ♀） 、雄虫（ ♂） 的 Ｒ Ｎ Ａ 和 Ｄ Ｎ Ａ 含量。另取经 Ａｒｔ 作用２４ ｈ 后的♀及♂虫体， 作体外培养２ ｈ 或４ ｈ ， 测定虫体对３ Ｈ 腺苷、［５ ３ Ｈ］ 尿苷和［ 甲基 ３ Ｈ］ 胸苷的摄入量以及上述３ Ｈ 标记核苷摄入虫体核酸的量。结果： 经 Ａｒｔ 体内作用４８ ｈ 后， 血吸虫♀虫的 Ｒ Ｎ Ａ 和 Ｄ Ｎ Ａ 含量分别较对照组减少５１６ ％ 和２３５ ％ ， 差异均显著， 而♂虫 Ｒ Ｎ Ａ 含量减少４２４ ％ 。♀及♂虫体经 Ａｒｔ 作用后移置体外培养２ｈ 或４ ｈ ， ♀虫对３ 种３ Ｈ 标记核苷的摄入量均较对照组的明显为少， 减少率达３５２ ％ ～５０１ ％ 。体外培养２ ｈ ，［ 甲基 ３ Ｈ］ 胸苷掺入♀虫 Ｄ Ｎ Ａ 的量较对照组减少７１４ ％ ， 培养４ ｈ 后， ［３ Ｈ］ 腺苷掺入♀虫 Ｒ Ｎ Ａ 和 Ｄ Ｎ Ａ 的量较对照组减少６５２ ％ 与５００ ％ 。结论： Ａｒｔ 对日本血吸虫， 尤其是♀虫的核酸代谢有抑制作用。     

蒿甲醚或吡喹酮早期治疗感染血吸虫尾蚴兔和犬的肝脏显微镜检查(英文)

目的:观察感染血吸虫尾蚴后早期用蒿甲醚(Art)或吡喹酮(Pra)治疗,对宿主肝组织的影响。方法:犬感染198-202条尾蚴后d7ig Art 10 mg·kg~(-1),Art胶囊(ArtC)15mg·kg~(-1)或感染后d 21ig Pra 30-40 mg·kg~(-1),1—2 wk重复给药1次,共2—4次;兔每隔日感染48—52条尾蚴,共5次,并于第1次感染后d7或d 21 ig上述剂量的Art和Pra,停药后4—5wk剖杀取肝作切片观察。结果:犬与兔经Art或Pra早期治疗后,减♀虫率达92.1％—100％,肝切片中的总虫卵肉芽肿数分别减少70.9％—97.3％和76.5％—97.4％,肝叶结构和肝索排列正常。结论:2种药物早期治疗对宿主肝脏有保护作用。     

高效液相质谱联用法测定人血浆中蒿甲醚及其活性代谢物双氢青蒿素的浓度

目的建立高效液相质谱联用法以测定人血浆中蒿甲醚(ARM)及其活性代谢物双氢青蒿素(DHA)的浓度.方法色谱条件色谱柱为C18(150 mm×4.6 mm,5μm),流动相为0.2%醋酸-甲醇梯度洗脱系统,流速为1.0 mL·min-4.质谱条件大气压化学电离方法(APCI)采集正离子,SIM方式对ARM和DHA检测m/z 221,对内标(青蒿素)检测m/z 283.血浆样品的预处理采用甲基叔丁基醚萃取法.结果ARM和DHA的线性范围为5～300μg·L-1,相关系数r＞0.999 0,检测限均为2μg·L-11.ARM和DHA日内和日间测定的RSD＜9.3%,回收率在92%～105%的范围内,提取回收率为80%～96%.结论该法简便、准确、灵敏、专属,适用于ARM和DHA的人体药动学研究.     

蒿甲醚治疗恶性疟疾现症病人83例

恶性疟疾现症病人108例,其中83例(男56例,女27例;年龄25±14yr)用蒿甲醚80mg,im,qd(首剂加倍)5d为一个疗程;儿童用量递减;其中有脑型恶性疟1例,并发黑尿热者3例;临床治愈率100％,退热时间为37±24h,平均疟原虫无性体转阴时间为47±20h,35d内的复燃率达13％。另外20例用青蒿琥酯60mg,iv,qd(首剂加倍)4d为一个疗程,疗效与蒿甲醚相似。