Simultaneous Analysis of 6-Mercaptopurine, 6-Methylmercaptopurine, and 6-Thioguanosine-5’-monophosphate in Dried Blood Spot Using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry

6-Mercaptopurine is a chemotherapeutic agent of the antimetabolite class. This study aims to analyze simultaneous validation of 6-mercaptopurine (6-MP), 6-methylmercaptopurine (6-MMP), and 6-thioguanosine-5’- monophosphate (6-TGMP) in dried blood spot (DBS) using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). An accurate volume of 60 μL blood was spotted onto DBS-CAMAG paper and then extracted using methanol 90% (v/v) containing an internal standard of 5-fluorouracil (5-FU). Separation was performed using a Waters Acquity UPLC BEH AMIDA column 1.7 μm (2.1 x 100 mm) with a mobile phase mixture of 0.2% (v/v) formic acid in water−0.1% (v/v) formic acid in acetonitrile-methanol with gradient elution and flow rate of 0.2 mL/min. Mass detection was done using Waters Xevo TQD with positive electrospray ionization (ESI) for 6-MP, 6-MMP, 6-TGMP and negative ESI for 5-FU, in multiple reaction monitoring mode. Detection rates of 6-MP, 6-MMP, 6-TGMP and 5-FU were m/z 153.09 > 119.09; 167.17 > 126.03; 380.16 > 168.00); 129.09 > 42.05, respectively. This method is linear across the range of 25.5–1020 ng/mL for 6-MP, 6-MMP and 6-TGMP. This method is valid for the in vitro simultaneous analysis of 6-MP, 6-MMP and 6-TGMP in DBS, based on European Medicine Agency guidelines

Manajemen Resiko Kestabilan Lereng Menggunakan Radar

Early Warning System (EWS) sangat diperlukan untuk mendeteksi secara dini suatu kejadian yang bisa menimbulkan dampak negatif. EWS juga sangat diperlukan dalam hal pemantauan kestabilan lereng bilamana pada lereng tersebut terdapat banyak aktivitas. Sehingga diperlukan suatu alat yang bisa mendeteksi hal tersebut dan bisa memberikan informasi secepatnya sehingga dampak negatif bisa dihindari. Sistem radar diharapkan mampu memberikan informasi suatu kondisi ketidakstabilan lereng sehingga ketika lereng terjadi pergerakan akan bisa terdeteksi. Dengan adanya radar manajemen resiko bisa dibuat dan dipraktekan dilapangan. Hal ini menjadi penting dimana tidak semua alat bisa mampu memberikan data secara up to date (real time) yang artinya saat terjadi indikasi ketidakstabilan pada saat ini juga muncul tanda bahaya pada monitor pengamat. Selain itu penentuan parameter tanda bahaya yang akan muncul pada layar monitor juga menjadi sangat penting mengingat kegagalan penentuan parameter ini juga akan membuat gagalnya radar sebagai Early Warning System. Dari hasil penelitian lihat bahwa radar mampu memberikan informasi ketidakstabilan dari angka yang kecil (4 pixel, 2mm dalam 2jam) dan pemilihan parameter tanda alarm sudah sangat tepat Sehingga manajemen resiko bisa tercapai dengan berhasilnya di aplikasikan dilapangan. Komunikasi juga menjadi bagian penting manajemen resiko ketika tanda bahaya muncul pada layar radar monitor

GLOBAL SALAFISM (Perspektif Pemikiran Roel Meijer, P.hD)

Islam represent religion which is multidimension, so that Islam can be seen and studied in so many sides which finally studied totally (Kaffah), hence it will yield a conclusion of islam which is paradocsal, so that if conducting an mistake of approach and by mistake of read pattern to Islam, hence which in yielding exactly a product of idea of productive counter of Islam, and even frequently strengthen impression of negative face of appearance to Islam. And conducted effort and also effort rather than yielding a progress of civilization and beautify Islam face appearance which is inklussive, however progressively strengthen to jell impressively that vision of Islam face which is ekslusive and impress preacher of medial terror of the world society. Islam is very wide religion, so that in comprehending and studying about Islam world hence tend to yield a conclusion which ispardocsa lbetween which is one with other. Its meaning do a wrong near byness to Islam, hence it will yield a conclusion which is also wrong . In context of is understanding of in perpective of Roel Meijer, global movement of moslem world cleft salafism have given separate colour and pattern to Islam people, and represent khasanah properties of Islam people in perpective of understanding of them to a knowledge of religious. At least there are three specifications of it in understanding of salafism in religion, one of the other is a problem of Doctrine of religion, and then political side, and from side of jihad in salafi perspektive

Quantification of 6-Mercaptopurine and Its Metabolites in Patients with Acute Lympoblastic Leukemia Using Dried Blood Spots and UPLC-MS/MS

This research aimed to quantitatively bioanalyze 6-mercaptopurine (6-MP), 6-methylmercaptopurine (6-MMP), and 6-thioguanosine-50 -monophosphate (6-TGMP) in dried blood spots (DBS) prepared from a small volume of acute lymphoblastic leukemia (ALL) patients. Analytes on the DBS card were extracted using 90% methanol with 5-fluorouracil (5-FU) as an internal standard. Analytical separation was performed on a Waters Acquity® UPLC BEH AMIDA column of 1.7 μm (2.1 × 100 mm) with a mobile phase mixture of 0.2% formic acid in water and 0.1% formic acid in acetonitrile-methanol, with gradient elution and a flow rate of 0.2 mL/min. Mass detection of 6-MP, 6-MMP, 6-TGMP, and 5-FU showed m/z values of 153.09 > 119.09, 167.17 > 126.03, 380.16 > 168.00, and 129.09 > 42.05, respectively. This DBS method had a run time of 5 min and yielded a linear calibration curve over a range of 25.5–1020 ng/mL for 6-MP, 6-MMP, and 6-TGMP. Analyte analysis in 22 of 24 ALL patients showed that the measured value of 6-TGMP as an active metabolite was in the range of 29–429 pmol/8 × 108 erythrocytes. Five of 22 patients had concentrations in a therapeutic range, which indicates that the treatment is effective, while 17 of 24 patients had concentrations below the therapeutic range, which indicates that a treatment dose adjustment is needed. The measured value of 6-MMP, an inactive metabolite, was in the range of 28–499 pmol/8 × 108 erythrocytes, which includes concentrations below the hepatotoxic range. The method employed here can thus be effectively utilized to support therapeutic drug monitoring