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Abstrak :
Skripsi ini membahas pelaksanaan pengetatan remisi narapidana korupsi di Lapas Sukamiskin Bandung pasca uji materiil Peraturan Pemerintah No. 99 Tahun 2012 tentang Perubahan Kedua Atas Peraturan Pemerintah Nomor 32 Tahun 1999 tentang Syarat dan Tata Cara Pelaksanaan Hak Warga Binaan Pemasyarakatan di Mahkamah Agung dan uji materiil Undang-Undang No. 12 Tahun 1995 tentang Pemasyarakatan di Mahkamah Konstitusi yang diajukan narapidana korupsi. Penelitian ini adalah penelitian yuridis normatif dengan pendekatan kualitatif untuk menganalisis pelaksanaan pengetatan remisi narapidana korupsi di Lapas Sukamiskin Bandung pasca uji materiil di Mahkamah Agung dan Mahkamah Konstitusi. Berdasarkan hasil penelitian yang dilakukan, pengetatan remisi narapidana korupsi yang diatur dalam PP 99 Tahun 2012 oleh narapidana korupsi dinilai bertentangan dengan hak-hak narapidana yang diatur dalam UU Pemasyarakatan. Setelah langkah uji materiil dilakukan narapidana korupsi di Mahkamah Agung dan Mahkamah Konstitusi ditolak, maka pelaksanaan pengetatan remisi narapidana korupsi di Lapas Sukamiskin Bandung dilakukan berdasarkan aturan perundang-undangan yang berlaku. Dari 366 narapidana korupsi di Lapas Sukamiskin, hanya 36 orang narapidana yang mendapatkan remisi. Sebanyak 30 orang mendapatkan remisi sebelum keluarnya PP 99 Tahun 2012 sehingga mereka tidak dikenai pengetatan syarat remisi. Sedangkan hanya 6 orang yang mendapatkan remisi pasca pengetatan yang diatur dalam PP. 99 Tahun 2012 yaitu memenuhi syarat menjadi justice collaborator dan membayar lunas denda dan uang pengganti.

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This thesis discuss the implementation of the tightening of remission for corruption prisoners at Sukamiskin Prison after material review in the Supreme Court against Government Regulation Number 99 Year 2012 on the Second Amendment of Government Regulation Number 32 Year 1999 on Conditions and Mechanisms for the Implementation of the Rights of Prisoners (PP 99 Year 2012) and another material review submitted by corruption prisoners in the Constitutional Court against Law Number 12 Year 19995 on Correction (Correction Law). The nature of the research is normative juridical with qualitative approve to analyze the implementation of tightening remission for remission for corruption prisoners at Sukamiskin Prison after those material reviews in the Supreme Court and the Constitutional Court. The result of this research shows that in the view of corruption prisoners the policy to tighten remission for corruption prisoners regulated in PP 99 Year 2012 contradicts with the rights of the prisoners regulated in the Correction Law. After both material reviews in the Supreme Court and in the Constitutional Court has failed, the policy of the tightening remission for corruption prisoners at Sukamiskin Prison in Bandung is implemented according to the applied rules and regulations. Out of 366 corruption prisoners at Sukamiskin Prison, there are only 36 prisoners who have received remission. However, 30 prisoners received the remission before PP 99 Year 2012 being issued so that the tightening remission policy was not applied for them. Meanwhile, only 6 prisoners were able to receive remission after the tightening policy in PP 99 Year 2012 was implemented, because they were qualified as justice collaborators and has paid fine penalties as well as fine replacements.

Abstrak :
6-Merkaptopurin (6-MP) merupakan agen kemoterapi kanker yang termasuk dalam golongan antimetabolit antagonis purin. 6-Merkaptopurin harus melalui jalur metabolisme oleh tiopurin S-metiltransferase (TPMT) untuk menjadi metabolit inaktifnya, yaitu 6-metilmerkaptopurin (6-MMP) untuk mengurangi efek sitotoksik dari 6-MP yang dapat menyebabkan mielosupresi. Penelitian ini bertujuan untuk memperoleh metode optimum dan tervalidasi dalam menganalisis 6-MP dan 6- MMP secara simultan dalam sampel Dried Blood Spot menggunakan kromatografi cair kinerja ultra tinggi tandem spektrometri massa. Larutan kontrol kualitas dan kurva kalibrasi dibuat dengan menotolkan masing-masing sebanyak 40 μL pada kertas CAMAG DBS dan dikeringkan selama 3 jam. Kertas DBS dipotong dengan diameter 8 mm dan diekstraksi dengan larutan asetonitril-metanol (1:3) yang mengandung baku 5-fluorourasil (5-FU). Pemisahan dilakukan dengan kolom Waters Acquity UPLC Class BEH C18 1,7 μm (2,1 x 100 mm) dengan fase gerak berupa asam format 0,1% dalam air - asam format 0,1% dalam asetonitril dengan gradient elusi dan laju alir 0,2 mL/menit. Deteksi massa dilakukan dengan Waters Xevo TQD dengan Electrospray Ionization (ESI) positif untuk 6-MP dan 6-MMP dan ESI negative untuk 5-FU pada mode Multiple Reaction Monitoring. Deteksi 6- MP, 6-MMP, 5-FU berturut-turut adalah 153,09 > 119,09; 167,17 > 126,03; 129,09 > 42,05. Metode ini linear dalam rentang 26 ? 1000 ng/mL untuk 6-MP dan 13 - 500 ng/mL untuk 6-MMP dengan r berturut-turut adalah ≥ 0,998 dan ≥ 0,999. Nilai % diff dan koefisien variasi (KV) untuk akurasi dan presisi intra hari dan antar hari tidak lebih dari 15% dan tidak lebih dari 20% pada konsentrasi LLOQ. Metode ini memenuhi persyaratan selektivitas, linearitas, akurasi, presisi, carry-over, dan efek matriks yang mengacu pada EMEA Guidelines. ...... 6-Mercaptopurine (6-MP) is a cancer chemotherapeutic agent that belongs to a class of purine antagonist antimetabolite. 6-Mercaptopurine has to go through the metabolic pathway by thiopurine S-methyltransferase (TPMT) to become its inactive metabolite, 6-methylmercaptopurine (6-MMP) to reduce the cytotoxic effect of 6-MP which can cause myelosuppression. This study aimed to obtain an optimum and validated method in analyzing 6-MP and 6-MMP simultaneously in Dried Blood Spot samples using ultra high-performance liquid chromatography tandem mass spectrometry. The quality control and calibration curves solutions were made by respectively spot 40 μL at DBS CAMAG paper and dried for 3 hours. DBS papers were cut with a diameter of 8 mm and extracted with acetonitrilemethanol (1:3) containing internal standard 5-fluorouracil (5-FU). Separation was performed with Waters Acquity UPLC BEH C18 column Class 1.7 μm (2.1 x 100 mm) with a mobile phase consists of 0.1% formic acid in water ? 0.1% formic acid in acetonitrile with gradient elution and flow rate 0.2 mL/minute. Mass detection was done using Waters Xevo TQD with positive electrospray ionization (ESI) for 6-MP and 6-MMP and negative ESI for 5-FU in Multiple Reaction Monitoring mode. Detection of 6-MP, 6-MMP, 5-FU respectively was 153.09> 119.09; 167.17> 126.03; 129.09> 42.05. This method is linear with the range 26-1000 ng / mL for 6-MP and 13 to 500 ng / mL for 6-MMP with consecutive r value is ≥ 0,998 and ≥ 0,999. % Diff value and coefficient of variation (CV) for accuracy and precision of intra-day and inter-day are not more than 15% and not more than 20% at a concentration LLOQ. This method fulfilled the requirements of selectivity, linearity, accuracy, precision, carry-over, and matrix effects which refers to the EMEA Guidelines.

Abstrak :
Siklofosfamid merupakan obat antikanker berupa pro-drug yang diaktifkan oleh enzim sitokrom P450 menjadi 4-hidroksisiklofosfamid 4-OHCP. Kadar 4-OHCP dalam tubuh dapat menggambarkan pembentukan fosforamid mustar yang dapat mengalkilasi DNA dan memberikan efek sitotoksik terhadap sel kanker. Analisis siklofosfamid dan 4-OHCP dilakukan pada Dried Blood Spot DBS 17 pasien kanker Rumah Sakit Kanker Dharmais yang diberikan rejimen siklofosfamid secara KCKUT-SM/SM sebagai upaya pemantauan terapi obat. Pengambilan darah dilakukan pada jam ke-2 dan ke-4 setelah pemberian kemoterapi melalui ujung jari. Hasil validasi metode bioanalisis parsial menghasilkan akurasi dan presisi intra hari dengan diff dan koefisien variasi KV tidak lebih dari 15 dan tidak lebih dari 20 pada konsentrasi LLOQ. Kurva kalibrasi yang linear didapat pada rentang 50-30.000 ng/mL untuk siklofosfamid dan 10-1000 ng/mL untuk 4- OHCP. Metode ini telah memenuhi syarat akurasi dan presisi intrahari sesuai European Medicines Agency EMEA tahun 2011. Hasil analisis pada 17 pasien kanker menunjukkan kadar siklofosfamid berkisar antara 6045,980 ng/mL hingga 37024,403 ng/mL dan 4-OHCP berkisar antara 33,155 ng/mL hingga 246,362 ng/mL. Hasil yang diperoleh dapat menjadi salah satu parameter pemantauan terapi siklofosfamid. ...... Cyclophosphamide is an anticancer in the form of prodrug activated by cytochrome P450 enzyme into 4 hydroxycyclophosphamide 4 OHCP. 4 OHCP levels in the body can describe formation of phosphoramide mustard that can alkylate DNA and give cytotoxic effects to cancer cells. Analysis of cyclophosphamide and 4 OHCP was performed on 17 Dried Blood Spots DBS of cancer patients who received cyclophosphamide as chemotherapy regiment from Dharmais Cancer Hospital by KCKUT SM SM for therapeutic drug monitoring. Samples were taken at 2nd and 4th hours after drug administration with finger prick method. The results of partial validation method produced intra day accuracy and intra day precision with diff and coefficient of variation CV were not more than 15 and not more than 20 in LLOQ concentration. Linear calibration curves were obtained in the range of 50 ndash 30,000 ng mL for cyclophosphamide and 10 1000 ng mL for 4 OHCP. This method has been fulfilled for intra day accuracy and precision according to European Medicines Agency EMEA Guidelines, 2011. The results of the 4 OHCP concentration analysis in 17 cancer patients showed that cyclophosphamide levels ranging from 6045.980 ng mL to 37024.403 ng mL and 4 OHCP was in the range of 33.155 ng mL to 246.362 ng mL. The results could be one of the monitoring parameters of cyclophosphamide therapy.

Abstrak :
Akrilamida adalah bahan kimia yang dapat terbentuk dalam makanan kaya karbohidrat akibat adanya proses pemanasan dengan suhu tinggi diatas 120°C. Saat ini, sudah banyak penelitian yang membahas efek toksisitas dan karsinogenisitas dari akrilamida seperti neurotoksik, genotoksik, dan sitotoksik. Di dalam tubuh, akrilamida dimetabolisme dengan bantuan enzim CYP2E1 menjadi senyawa epoksida, yaitu glisidamida. Akrilamida dan glisidamida sangat reaktif terhadap DNA dan dapat membentuk DNAadduct, yang bersifat genotoksik dan sitotoksik. Glisidamida diketahui memiliki afinitas yang lebih tinggi terhadap DNA dibandingkan dengan prekursornya, sehingga dapat dikatakan bahwa glisidamida merupakan karsinogen utama dari akrilamida. Paparan akrilamida pada manusia dapat berasal dari paparan pekerjaan, makanan, dan asap rokok. Namun, makanan merupakan sumber paparan utama. Untuk mengetahui risiko paparan akrilamida dan glisidamida terhadap manusia dari makanan maka perlu dilakukan analisis kadar dalam darah. Salah satu metode bioanalisis yang dapat digunakan yaitu dengan metode biosampling Dried Blood Spot (DBS). Analisis kadar dilakukan menggunakan Kromatografi Cair Kinerja Ultra Tinggi Tandem Spektrometri Massa (KCKUT-SM/SM). Skripsi ini bertujuan untuk mengkaji metode bioanalisis yang sesuai untuk digunakan dalam analisis akrilamida dan glisidamida dalam DBS dengan KCKUT-SM/SM. Selain itu, perlu juga dilihat hubungan antara pola makan dengan kadar akrilamida dalam darah serta mengetahui potensi karsinogenisitas kedua analit tersebut terhadap manusia, terutama glisidamida. ......Acrylamide is a chemical compound that formed when carbohydrate-rich food is placed in the heating process with high temperatures above 120°C. Many studies have discussed the toxicity and carcinogenicity effects of acrylamide which produced neurotoxin, genotoxin, and cytotoxin. After ingestion, acrylamide undergoes metabolism which catalyzed by the CYP2E1 enzyme into its epoxide compounds, glycidamide. Both acrylamide and glycidamide are very reactive to DNA and can form DNA-adducts, which are known to be genotoxic and cytotoxic. Glycidamide is known to have a higher affinity for DNA compared to its precursors, so it can be said that glycidamide is the ultimate carcinogen of acrylamide. Exposure to acrylamide in humans can be obtained from a few factors, which are occupational exposure, food exposure, and cigarette smoke. However, studies found out that dietary intake is the major source of acrylamide and glycidamide exposure. To determine the risk of acrylamide and glycidamide exposure to humans from dietary intake, it is necessary to analyze its concentration levels in the blood. One of the biosampling methods that can be used is Dried Blood Spot or DBS. The quantitative analysis was conducted using Liquid Chromatography-Tandem Mass Spectrometry (LCMS/ MS). This review article aims to analyze the bioanalytical method that is most suitable for the analysis of acrylamide and glycidamide in DBS using LC-MS/MS. Furthermore, it is necessary to examine the relationship between dietary intake with acrylamide and glycidamide levels in the blood, as well as knowing the potential carcinogenicity of both analytes to humans, especially glycidamides.

Abstrak :
Asap rokok adalah sumber utama paparan akrilamida setelah makanan. Akrilamida diklasifikasikan sebagai senyawa berpotensi karsinogenik pada manusia (Grup 2A). Akrilamida dimetabolisme oleh enzim CYP2E1 menjadi glisidamida yang sangat reaktif terhadap DNA dan dapat membentuk DNA adduct sehingga menyebabkan efek karsinogenik pada manusia. Kadar akrilamida dalam asap rokok berkisar 1,000–7,991 μg/rokok yang dipengaruhi perbedaan merek rokok. Paparan akrilamida pada perokok 2,2–4,6 kali lebih tinggi daripada non perokok dan glisidamida 1,1–3,8 kali lebih tinggi daripada non perokok. Kadar akrilamida dan glisidamida dalam sampel Dried Blood Spot (DBS) belum diketahui. Keunggulan DBS yaitu nyaman bagi subjek, volume sampel kecil, analit lebih stabil, penyimpanan dan transportasi mudah, serta preparasi sampel sederhana. Aplikasi volumetrik menggunakan pipet volumetrik atau perangkat modern seperti microfluidic DBS dapat mengatasi efek hematokrit darah. Metode KCKUT-SM/SM dapat mengkuantifikasi sejumlah kecil analit karena menghasilkan pemisahan yang baik, waktu retensi cepat, sensitivitas dan selektivitas tinggi. Validasi metode serta analisis akrilamida dan glisidamida dalam sampel DBS perokok secara KCKUT-SM/SM penting dilakukan untuk mengukur risiko paparan akrilamida melalui asap rokok. Metode analisis menggunakan KCKUT-SM/SM dengan kolom Acquity® UPLC BEH C18; fase gerak asam formiat 0,1% dalam air-asetonitril (40:60 v/v) dengan elusi gradien; laju alir 0,20 mL/menit; deteksi massa menggunakan penganalisis massa triple quadrupole dengan mode Electrospray Source Ionization (ESI) positif tipe Multiple Reaction Monitoring (MRM); nilai m/z 71,99>55,0; 87,9>44,2; 75>58,0 untuk akrilamida, glisidamida, dan d3-akrilamida. Preparasi sampel dengan pengendapan protein menggunakan larutan pengekstraksi metanol. ......Cigarette smoke is the major source of acrylamide exposure after food. Acrylamide is classified as a probably carcinogenic to humans (Group 2A). Acrylamide is metabolized by CYP2E1 enzyme into glycidamide that very reactive to DNA and can form DNA adducts causing carcinogenic effects in humans. Acrylamide level in cigarette smoke is around 1.000–7.991 μg/cigarette caused by different cigarette brands. Acrylamide exposure in smokers is 2.2–4.6 times higher than non-smokers and glycidamide exposure 1.1–3.8 times higher than non-smokers. The levels of acrylamide and glycidamide in Dried Blood Spot (DBS) sample are still unknown. Advantages of DBS are convenient for subjects, small sample volumes, analytes are more stable, easy storage and transport, and simple sample preparation. Volumetric application by using volumetric pipettes or modern devices such as microfluidic DBS are used to overcome blood hematocrit effect. UHPLC-MS/MS method can quantify small amounts of analytes due to good separation, fast retention time, high sensitivity and selectivity. Method validation and analysis of acrylamide and glycidamide in DBS smokers by UHPLC-MS/MS is important to measure the risk of acrylamide exposure through cigarette smoke. Analysis method using UHPLC-MS/MS with Acquity® UPLC BEH C18 column; mobile phase was 0.1% of formic acid in water and acetonitrile (40:60 v/v) with gradien elution; flow rate was 0.20 mL/min; mass detection using triple quadrupole mass analyzer with positive Electrospray Source Ionization (ESI) and Multiple Reaction Monitoring (MRM) type; m/z values were 71.99>55.0; 87.9>44.2; 75>58.0 for acrylamide, glycidamide, and acrylamide-d3. Sample preparation with protein precipitation using methanol as extraction solvent.

Abstrak :
Rifampisin merupakan antibiotik yang biasa dikonsumsi bersamaan dengan isoniazid dalam bentuk kombinasi dosis tetap yang digunakan sebagai regimen terapi dalam pengobatan tuberkulosis. Resistensi bakteri dapat terjadi apabila kadar rifampisin berada di bawah rentang terapi, yaitu 8 – 24 μg/mL setelah pemberian dosis oral 600 mg. Oleh karena itu perlu dilakukan pemantauan kadar obat untuk mencapai keberhasilan terapi. Beberapa metode analisis rifampisin menggunakan plasma dan Dried Blood Spot telah dikembangkan dan divalidasi. Penelitian ini bertujuan untuk mengembangkan metode analisis rifampisin yang tervalidasi dalam Volumetric Absorptive Microsampling (VAMS) menggunakan kromatografi cair kinerja ultra tinggi – tandem spektrometri massa. Penelitian ini menggunakan VAMS karena tekniknya yang sederhana dan lebih nyaman, volume pengambilan yang lebih sedikit, serta tidak adanya efek hematokrit. Metode preparasi sampel dilakukan dengan cara pengendapan protein menggunakan metanol-asetonitril 1:2 sebanyak 500 μL dan dianalisis menggunakan kromatografi cair kinerja ultra tinggi dengan detektor spektrometri massa dengan mode electrospray ionization positif dan multiple reaction monitoring pada m/z 823,48 > 791,76 untuk rifampisin, dan m/z 370,35 > 288,28 untuk silostazol sebagai baku dalam. Kondisi analisis optimum diperoleh menggunakan kolom Acquity® UPLC BEH C18 (2,1 x 100 mm; 1,7 μm); laju alir 0,10 mL/menit; fase gerak asam format 0,1% dan metanol (20:80), suhu kolom 40°C, dengan volume injeksi 10 μL. Nilai LLOQ yang didapatkan adalah 0,4 μg/mL untuk rifampisin dengan rentang kurva kalibrasi 0,4 – 30 μg/mL. Metode analisis telah tervalidasi sesuai dengan kriteria persyaratan yang ditetapkan oleh US Food and Drug Administration (2018) dan European Medicines Agency (2011). ......Rifampicin is an antibiotic that is usually taken together with isoniazid in the form of a fixed-dose combination that is used as a therapeutic regimen in the treatment of tuberculosis. Bacterial resistance can occur if the levels of rifampicin and isoniazid are below the therapeutic range, which is 8 – 24 μg/mL after oral administration of 600 mg dose. Therefore, it is necessary to monitor drug levels to achieve therapeutic goals. There are several analytical methods of rifampicin using plasma and Dried Blood Spot have been developed and validated. This research aims to develop a validated analysis method of rifampicin in Volumetric Absorptive Microsampling (VAMS) using UHPLC- MS/MS. This research used VAMS because the technique is simpler and more convenient, requires small volume of samples, and not affected the hematocrit effect. The sample preparation in VAMS extracted using protein precipitation method using 500 μL of methanol – acetonitrile 1:2 and analyzed using liquid chromatography with mass spectrometry detector and positive electrospray ionization and multiple reaction monitoring with m/z 823,48 > 791,76 for rifampicin, and m/z 370,35 > 288,28 for cilostazol. Optimum analytical conditions were obtained using the Acquity® UPLC BEH C18 column (2.1 x 100 mm; 1.7 m); flow rate 0.10 mL/min; mobile phase 0.1% formic acid and methanol (20:80), column temperature 40°C, and injection volume of 10 μL. The LLOQ value obtained was 0,4 μg/mL for rifampicin with a calibration curve range of 0,4 – 30 μg/mL. The analytical method has been validated in accordance with the requirements criteria set by the US Food and Drug Administration (2018) and the European Medicines Agency (2011).

Abstrak :
Ivermectin merupakan obat antihelmintik berspektrum luas yang digunakan untuk mengendalikan penyakit onchocerciasis dari parasit nematoda. Sebagai obat cacing, ivermectin didisain untuk memiliki kadar yang tinggi di saluran cerna, sehingga yang masuk sistemik tergolong rendah. Oleh karena kadar ivermectin yang sangat kecil, dibutuhkan metode yang sensitif dan selektif untuk analisis ivermectin dalam darah. Beberapa metode telah dikembangkan menggunakan plasma dan Dried Blood Spot, namun masih terdapat kekurangan karena terdapat efek hematokrit. Oleh karena itu, penelitian ini bertujuan untuk mengembangkan metode analisis ivermectin yang tervalidasi dengan baku dalam doramectin menggunakan Kromatografi Cair Kinerja Ultra Tinggi – tandem Spektrometri Massa (KCKUT-SM/SM). Deteksi menggunakan spektrometri massa triple quadrupole dengan mode electrospray ionization (ESI) positif. Matriks biologis yang digunakan yaitu darah utuh dalam Volumetric Absorptive Microsampling (VAMS), kemudian dipreparasi menggunakan metode pengendapan protein dengan campuran asetonitril dan metanol (1:1). VAMS dipilih karena tidak terdapat efek hematokrit, dibutuhkan volume sampel yang sedikit dan akurat, serta pengambilannya lebih efisien. Kondisi analisis optimum diperoleh menggunakan kolom Acquity® UPLC BEH C18 (2,1 x 100 mm; 1,7 m); fase gerak amonium format 5 mM pH 3 dan asetonitril (10:90); laju alir 0,2 mL/menit; mode elusi isokratik selama 5 menit dengan suhu kolom 50˚C; deteksi menggunakan Multiple Reaction Monitoring (MRM) pada nilai m/z 892,41 > 569,5 untuk ivermectin dan 916,41 > 331,35 untuk doramectin. Metode analisis telah tervalidasi seluruhnya mengikuti pedoman dari US Food and Drug Administration tahun 2018. Nilai LLOQ 1 ng/mL dengan rentang konsentrasi linear pada 1 - 150 ng/mL ......Ivermectin is a broad-spectrum anthelmintic used to control onchocerciasis from nematode parasites. As an anthelmintic, ivermectin is designed to have high levels in the gastrointestinal tract, so that the systemic intake is relatively low. Due to the very small concentration of ivermectin, a sensitive and selective method is needed for the analysis of ivermectin in blood. Several methods have been developed using plasma and Dried Blood Spots, but there are still shortcomings due to hematocrit effects. Therefore, this study was conducted to develop a validated ivermectin analysis method with doramectin as the internal standard in using Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry. The analysis was performed using a triple quadrupole mass spectrometry with positive electrospray ionization (ESI) mode. The biological matrix used whole blood in Volumetric Absorptive Microsampling (VAMS) and extracted using the protein precipitation method with mixture of acetonitrile and methanol (1:1). VAMS has some advantages such as not affected by hematocrit, requires small and fixed volume of sample, also more efficient sampling process. The optimum conditions were obtained using the Acquity® UPLC BEH C18 column (2.1 x 100 mm; 1,7 m); flow rate was 0,2 mL/min; mobile phase was ammonium formate 5 mM pH 3 and acetonitrile (10:90); isocratic elusion for 5 minutes; Multiple Reaction Monitoring (MRM) detection with m/z values were 892.41 > 569.5 for ivermectin and 916,41 > 331,35 for doramectin. The method has been fully validated following the guidelines from US FDA (2018). LLOQ value was 1 ng/mL with a linear concentration range of 1 – 150 ng/mL.

Abstrak :
Ivermectin merupakan obat yang telah disetujui FDA untuk digunakan pada Strongyloidiasis dan Onchocerciasis, yaitu dua kondisi yang disebabkan oleh cacing parasit. Namun ivermectin banyak disalahgunakan sebagai obat COVID-19 yang sebenarnya membutuhkan dosis berkali lipat agar konsentrasi plasma yang dibutuhkan untuk efikasi antivirus tercapai. Oleh karena itu, perlu dilakukan uji profil farmakokinetika untuk mengetahui keamanan, efikasi, serta toksisitas suatu obat. Pengujian ini dilakukan dengan menganalisis kadar ivermectin pada plasma 6 orang subjek Indonesia sehat yang telah mengonsumsi tablet ivermectin 12 mg secara oral menggunakan Kromatografi Cair Kinerja Ultra Tinggi Tandem Spektrometri Massa (KCKUT-SM/SM). Pengambilan darah subjek dilakukan sebanyak 16 titik pada beberapa interval waktu hingga jam ke-72. Kondisi kromatografi yang digunakan adalah kolom Acquity UPLC BEH C18 (2,1 x 100 mm x 1,7 µm); suhu kolom 40oC; fase gerak amonium format 5 mM pH 3 – asetonitril dengan perbandingan 10:90; laju alir 0,2 mL/menit; dan doramectin sebagai baku dalam. Profil farmakokinetika dalam sampel plasma menghasilkan; AUC0-t 518,43 ± 71,89 ng/mL; AUC0- 582,92 ± 114,28 ng/mL; Cmaks 47,79 – 53,31 ng/mL; tmaks 4,50 ± 0,00 jam; dan t½ 23,15 ± 6,81 jam. Berdasarkan penelitian sebelumnya, Cmaks in vitro yang dibutuhkan untuk mematikan virus COVID-19 yaitu sebesar ± 5 µg/mL, apabila dibandingkan dengan Cmaks yang diperoleh pada penelitian ini, memperoleh kesimpulan bahwa konsentrasi untuk mematikan virus COVID-19 tidak tercapai. ......Ivermectin is a drug approved by FDA that used for Strongyloidiasis and Onchocerciasis, two conditions caused by parasitic worms. However, ivermectin is widely misused as a COVID-19 drug which requires multiple doses to achieve the plasma concentration required for antiviral efficacy. Therefore, it is necessary to test the pharmacokinetic profile to determine the safety, efficacy, and toxicity of the drug. This test was done by analizing the ivermectin levels in the plasma of 6 healthy Indonesian subjects who had taken 12 mg of ivermectin tablet orally by using Ultra High Performance Liquid Chromatography Tandem – Mass Spectrmetry (UHPLC-MS/MS). Subjects’ blood sampling was collected as many as 16 points at several time intervals up to 72 hours. The chromatographic conditions used was Acquity UPLC BEH C18 column (2.1 x 100 mm x 1.7 µm); 40oC column temperature; mobile phase consists of ammonium formate 5 mM pH 3 – acetonitrile with 10:90 comparison; 0,2 mL/minute flow rate; and doramectin as an internal standard. The pharmacokinetic profile in plasma results were; AUC0-t was 518,43 ± 71,89 ng/mL; AUC0- was 582,92 ± 114,28 ng/mL; Cmax ranged from 47,79 to 53,31 ng/mL; tmax was 4,50 ± 0,00 hours; and t½ was 23,15 ± 6,81 hours. Based on previous research, the in vitro Cmax required to kill the COVID-19 virus is ± 5 g/mL, when compared with the Cmax obtained in this study, it is concluded that the concentration to kill the COVID-19 virus was not achieved.

Abstrak :
Development and Validation of Cyclophosphamide and 4-Hydroxycyclophosphamide Quantification Method in Volumetric Absorptive Microsampling (VAMS) by Liquid Chromatography - Tandem Mass Spectrometry ......Cyclophosphamide is an anticancer alkylating prodrug, metabolized by CYP450 into its active metabolite, named 4-hydroxycyclophosphamide (4-OHCP). Its therapeutic effectiveness is determined by the 4-OHCP concentration. Several analytical methods using plasma and Dried Blood Spot have been developed to analyze cyclophosphamide and 4-OHCP. However, there are lots of disadvantages. Therefore, this study was conducted to develop a validated cyclophosphamide and 4-OHCP analysis method with 4-hydroxycyclophosphamide-d4 (4OHCP-d4) as the internal standard in Volumetric Absorptive Microsampling (VAMS) using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry. VAMS requires small volume of sample, is not affected by hematocrit, and more efficient sampling process. Sample preparation was started by derivatization with 5 μL semicarbazide hydrochloride to overcome the instability of 4-OHCP and 4-OHCP-d4, which was absorbed by VAMS. Afterwards, 25 μL samples were absorbed into VAMS and extracted using the protein deposition method with methanol. The analysis was performed using a triple quadrupole Mass Spectrometry with positive electrospray ionization mode. The optimum conditions were obtained using the Acquity® UPLC BEH C18 column (2.1 x 100 mm; 1.7 μm); flow rate 0.2 mL/min; mobile phase 0.01% formic acid and methanol; gradient elution mode for 6 minutes; multiple reaction monitoring detection with m/z values 260.65>140.03 for cyclophosphamide, 333.65>221.04 for 4-OHCP-SCZ, and 337.71>225.05 for 4-OHCP-d4-SCZ. The method has met the validation requirements set by the FDA (2018). Cyclophosphamide LLOQ value was 5 ng/mL and the calibration curve range was 5 - 60,000 ng/mL. Furthermore, 4-OHCP LLOQ value was 2.5 ng/mL and the calibration curve range was 2.5 - 1,000 ng/mL.

Abstrak :
Kurkumin merupakan senyawa polifenol yang umumnya terdapat pada rimpang kunyit (Curcuma longa L.). Setelah pemberian peroral, kurkumin dalam tubuh akan segera dimetabolisme melalui proses reduksi maupun konjugasi. Oleh karena itu, kadar kurkumin di dalam darah sangat kecil sehingga diperlukan metode bioanalisis yang selektif dan sensitif. Metode Kromatografi Cair Kinerja Ultra Tinggi ? Tandem Spektrometer Massa (KCKUT-SM/SM) yang spesifik dan cepat telah dikembangkan dan divalidasi untuk menetapkan kadar kurkumin dalam plasma manusia menggunkan diazepam sebagai baku dalam. Pemisahan dilakukan menggunakan kolom C18 Acquity® Waters, UPLC BEH 1,7 μm, 2,1 x 100 mm, fase gerak asam format 0,15% - Asetonitril (50:50), laju alir 0,5 mL/menit dengan metode preparasi sampel ekstraksi cair-cair menggunakan campuran larutan etil asetatmetanol (95:5). Mode ionisasi yang digunakan adalah multiple reaction monitoring (MRM) dengan mode Electrospray ionization positif dengan nilai m/z berturut-turut 369,05 > 176,95 dan m/z 284,95 > 193 untuk kurkumin dan diazepam. Metode bioanalisis menunjukkan presisi dan akurasi yang baik dengan nilai % KV dan % bias < 15% untuk semua konsentrasi (QCL, QCM dan QCH) dengan nilai kurva kalibrasi yang linear (r = 0,999) pada rentang 1 ? 100 ng/mL dan nilai LLOQ untuk senyawa kurkumin sebesar 1,0 ng/mL. Metode ini telah diaplikasikan untuk menentukkan kadar kurkumin dalam plasma 1 orang sehat yang telah diberi sediaan kurkumin 1800 mg. Dari penelitian diperoleh hasil tidak ditemukannya kurkumin dalam bentuk bebas, tetapi bentuk kurkumin terglukuronidasi dan tersulfatasi. Perbandingan antara jumlah terglukuronidasi dan tersulfatasi 4:1. Metode analisis yang diperoleh sudah memenuhi kriteria validitas menurut Guidance EMEA 2011 dengan sensitivitas yang tinggi sehingga dapat diaplikasikan untuk studi in-vivo. ...... Curcumin is a polyphenol, found in the spice turmeric from the rhizome of the herb Curcuma Longa. After oral administration, Curcumin undergoes rapid metabolism by conjugation and reduction. Curcumin levels are generally low so that the required bioanalytical method is selective and sensitive. A simple, specific and rapid UPLCMS/ MS method has been developed and validated for the estimation of curcumin in human plasma, using diazepam as internal standard (IS). The separation using UPLC BEH C18 column 1.7 μm, 2,1 x 100 mm Acquity® Waters; 0.15% formic acid - acetonitril (50:50, v/v) as mobile phase; flow rate 0.5 mL/min; using liquid-liquid extraction with the mixture of ethyl acetate-methanol (95:5) for the sample preparation. The ionization mode using electrospray ionization (ESI) detection in multiple reaction monitoring (MRM) in positive ionization mode. The MS/MS ion transitions monitored were m/z 369.05 >176.95 and 284.95 > 193 for curcumin and diazepam respectively. The method was proved to be precise and accurate (expressed as coefficient of variation, % CV and differentiation, % diif) was < 15% for all concentration (QCL, QCM and QCH) with a coefficient correlation ( r = 0.999) and linearity range of 1 ? 100 ng/mL, LLOQ for curcumin was 1 ng/mL. The Method was applicated to determine the level of curcumin in healthy subject after oral administration 1800 mg of curcumin dosage form. No Free curcumin was detected in plasma sample, but curcumin glucuronides and sulfates were detected in plasma subject. The ratio of glucuronide to sulfate was 4: 1. The analytical method fullfilthe criteria of validity by the EMEA Guidance 2011 with high sensitivity and it would be applicable to in-vivo study.