| Summary: | 碩士 === 高雄醫學大學 === 藥學研究所碩士班 === 93 === This study describes the methods established by capillary electrophoresis for analyzing nonsteroidal anti-inflammatory drugs in pharmaceuticals and sulindac and its two metabolites in plasma.
A simple capillary zone electrophoresis (CZE) method has been developed for analyzing seven nonsteroidal anti-inflammatory drugs (NSAIDs) including sulindac (SU), ketoprofen (KE), indomethacin (IN), piroxicam (PI), nimesulide (NI), ibuprofen (IB), and naproxen (NA). The separation was run using borate buffer (60 mM, pH 8.5) containing 13 % (v/v) methanol at 20 kV, and detected at 200 nm. Several parameters were studied, such as concentration and pH of borate buffer, methanol percentage, and separation voltage. In method validation, calibration plots were linear over the range 40.0 ~ 500.0 μM. In intra-day and inter-day analysis, relative standard deviations (RSD) and relative errors (RE) were all less than 5%. The limits of detection were 10.0 μM for SU, IN, PI, and 20.0 μM for KE, NI, IB, NA (S/N= 3, sampling 6 s by pressure, 50 mbar). All recoveries were greater than 95%. This method was applied for quality control of six NSAIDs in pharmaceuticals using NI as internal standard (IS). The assay results were within the labeled amounts required by USP 25.
Field-amplified sample stacking with EOF suppressant was used to determine sulindac (SU) and its two active metabolites, sulindac sulfide (SI) and sulindac sulfone (SO), in plasma. Separation was performed using phosphate buffer (40 mM, pH 5.5) containing 2, 6-di-O-methyl-β-CD (2.25 mM) and HEC (0.005 % (w/v)) as an EOF suppressant. The separation was set at -30 kV and 200 nm. The analytes were successfully extracted by toluene. In method validation, calibration plots were linear over the range 0.3 ~ 30.0 μM. In intra-day and inter-day analysis, relative standard deviations (RSD) and relative errors (RE) were all less than 9 %. The limits of detection were 0.1 μM for SU, SO and 0.3 μM for SI (S/N =4, sampling 99.9 s by electric–driven injection, -10 kV). All relative recoveries and absolute recoveries were greater than 94 % and 52 %, respectively. This method was feasible for determining SU and its metabolites in plasma. One female volunteer (27 yr, 42 kg) was orally administrated one SU tablet (Clinoril®, 200 mg) and drawn blood samples after 3 hours. After pretreatment and analysis, the plasma levels of SU, SI and SO were 11.8 μM, 3.2 μM, 3.1 μM, respectively.
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