Hidroksiklorokuin (HCQ) merupakan senyawa golongan kuinolin turunan dari klorokuin yang merupakan salah satu obat yang digunakan dalam terapi Lupus Eritematosus Sistemik (LES). Pada pengembangan dan validasi metode analisis hidroksiklorokuin, dilakukan evaluasi stabilitas hidroksiklorokuin jangka panjang secara in vitro. Namun, evaluasi stabilitas secara in vitro tidak mencerminkan proses metabolisme obat di dalam tubuh karena hidroksiklorokuin dimetabolisme secara enzimatik menjadi beberapa metabolit sehingga dibutuhkan evaluasi incurred sample stability. Penelitian ini dilakukan dengan tujuan mendapatkan profil farmakokinetika hidroksiklorokuin menggunakan Volumetric Absorptive Microsampling (VAMS) sebagai teknik microsampling yang aman digunakan selama pandemi COVID-19. Selain itu juga mengevaluasi stabilitas hidroksiklorokuin dalam Volumetric Absorptive Microsampling (VAMS) yang mengandung darah subjek sehat yang mengonsumsi tablet salut selaput hidroksiklorokuin sulfat 200 mg dengan melakukan evaluasi Incurred Sample Stability terhadap sampel hidroksiklorokuin pada 2 titik konsentrasi sekitar Cmaks dan 1 titik fase eliminasi di hari ke 7, 14 dan 30. Kondisi kromatografi yang digunakan adalah kolom C18 (Waters, Xbridge®; 250 × 4,6 mm; 5μm); fase gerak asetonitril-dietilamin 1% (65:35); laju alir 0,8 mL/menit; suhu kolom 45°C; panjang gelombang analisis detektor PDA 332 nm; volume penyuntikan 100 μL; baku dalam klorokuin; dan waktu analisis 12 menit. Profil farmakokinetika hidroksiklorokuin dalam sampel VAMS memberikan hasil konsentrasi maksimum (Cmaks) dari keenam subjek sehat berkisar antara 322,61 – 505,32 ng/mL dan rata-rata sebesar 425,33 ± 65,90 ng/mL; waktu puncak (tmaks) yang diperoleh dari keenam subjek sehat adalah 4 jam; rata-rata t1/2 sebesar 23,32 ± 9,65 jam; rata-rata AUC0-72 sebesar 5103,63 ± 1419,66 ng jam/mL; rata-rata AUC0-∞ sebesar 5763,97 ± 2155,26 ng jam/mL; dan perbandingan AUC di atas 80%. Incurred sample stability hidroksiklorokuin dalam VAMS enam subjek sehat hingga hari ke-30 menunjukkan hasil yang memenuhi persyaratan EMEA Bioanalytical Guideline tahun 2011 dengan harga %diff yang diperoleh tidak lebih dari 20% dari setidaknya 67% sampel yang dianalisis ulang.

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Hydroxychloroquine (HCQ) is a quinoline compound derived from chloroquine which is one of the drugs used in the treatment of Systemic Lupus Erythematosus (SLE). In the development and validation of the hydroxychloroquine analysis method, an in vitro evaluation of the long-term stability of hydroxychloroquine was carried out. However, in vitro stability evaluation does not reflect drug metabolism processes in the body because hydroxychloroquine is enzymatically metabolized into several metabolites, so an evaluation of the incurred sample stability is required. This study was conducted with the aim of obtaining a pharmacokinetic profile of hydroxychloroquine using Volumetric Absorptive Microsampling (VAMS) as a safe microsampling technique to use during the COVID-19 pandemic. Beside that also evaluating the stability of hydroxychloroquine in Volumetric Absorptive Microsampling (VAMS) containing the blood of healthy subjects taking 200 mg hydroxychloroquine sulfate film-coated tablets by evaluating the Incurred Sample Stability of hydroxychloroquine samples at 2 points of concentration around Cmax and 1 point of elimination phase on days 7, 14 and 30. The chromatographic conditions used were column C18 (Waters, XBridge®; 250 × 4.6 mm; 5μm); mobile phase consist of acetonitrile-1% diethylamine (65:35); flow rate of 0.8 mL/min; column temperature 45°C; PDA detector analysis wavelength of 332 nm; injection volume 100 μL; chloroquine as internal standard; and analysis time of 12 minutes. The pharmacokinetic profile of hydroxychloroquine in the VAMS samples showed that the maximum concentration (Cmax) of the six healthy subjects ranged from 322.61-505.32 ng/mL and an average of 425.33 ± 65.90 ng/mL; the peak time (tmax) obtained from the six healthy subjects was 4 hours; the average of t1/2 was 23.32 ± 9.65 hours; the average AUC0-72 was 5103.63 ± 1419.66 ng hour/mL; the average AUC0-∞ was 5763.97 ± 2155.26 ng hour/mL; and the AUC ratio is above 80%. The incurred sample stability of hydroxychloroquine in the VAMS of six healthy subjects up to day 30 showed results that met the requirements of the 2011 EMEA Bioanalytical Guideline with the %diff value obtained no more than 20% from at least 67% of the samples reanalyzed.