SummaryA simple, rapid and accurate, routine-HPLC method is described for simultaneous determination of acetaminophen, caffeine and chlorpheniramine maleate in a new tablet formulation. Chromatographic separation of the three pharmaceuticals was achieved on a Hypersil CN column (150 x 5.0 mm, 5 Ixm) using a mobile phase comprising a mixture of acetonitrile, an ion-pair solution and tetrahyclrofuran (13:14:8Z v/v, pH 4.5). The flow-rate was changed from 1.0 mL min 1 (in 0 ~ Z5 min) to 1.8 mL min 1 (after 3.5 min). Detection was 223 nm. Separation was complete in < 10 min. The method was validated for system suitability, hnearity, accuracy, precision, limits of detection and quantitation, and robustness. Linearity, accuracy and precision were found to be acceptable over the ranges 31.6 -315.8 Ixg mL 1 for acetaminophen, 9.5 -94.6 I~g mL 1 forcaffeine and 1.4-13.8 I~g mL 1 forchlorpheniramine maleate.

Ling-Gui-Zhu-Gan decoction (LGZGD), a well-known traditional Chinese medicine (TCM) formula, has been extensively used for the treatment of cardiovascular disease in clinic. However, the chemical constituents in LGZGD had not been investigated so far. In this study, an ultra performance liquid chromatography-hybrid electrospray ionization linear ion trap-Orbitrap mass spectrometry (UPLC-LTQ-Oribitrap-MS/MS) method was established for rapid separation and structural identification of the constituents in LGZGD. Separation was performed on an ACQUITY(TM) UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) by gradient elution mode, using acetonitrile-water containing 0.1% formic acid as mobile phase at the flow rate of 0.2 mL/min. Accurate mass measurement for molecular ions and characteristic fragment ions could represent identification criteria for these compounds. As a result, 95 compounds including triterpene acids, triterpene saponins, flavonoids, coumarins, coumestans, benzofurans, phenylpropanoids and sesquiterpenoid lactones were detected, and 90 of them were tentatively identified. All compounds were further assigned in the individual raw material. In conclusion, the UPLC-LTQ-Orbitrap-MS/MS is a highly efficient technique to separate and identify constituents in complex matrices of TCMs. These results obtained in this research will provide a basis for quality control and further in vivo study of LGZGD.

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Key WardsColumn hquicl chromatography Acetaminophen Pseucloepheclrine hyclrochloricle Dextromethorphen hyclrobromicle Cold formulation SummaryA rapid and accurate HPLC method is described for the simultaneous determination of acetaminophen, clextromethorphen hyclrobromicle and pseucloepheclrine hyclrochloricle in a new cold formulation. Chromatographic separation of the three pharmaceuticals was performed on a Hypersil CN column (150 • 5.0 mm, 5 Ixm) with a mobile phase mixture of an ion-pairing solution, methanol and acetonitrile (25:57:18, v/v), at a flow rate of 1.0 mL min 1, with detection at 220 nm. Separation was complete in less than 10 min. The method was vahclatecl for hnearity, accuracy, precision, limit of quantitation and robustness. Linearity, accuracy, and precision were found to be acceptable over the ranges of 2.06 ~ 20.6 I~g 9 mL 1 for acetaminophen, 0.202 ~ 2.02 mg 9 mL 1 for pseucloepheclrine hyclrochloricle and 0.042 1.06 mg 9 mL 1 forclextromethorphen hyclrobromicle.

Pharmacokinetics of a new sustained-release formulation of theophylline sodium glycerinate in healthy subjects was studied. In this study, a new asymmetric dosage regimen was presented to achieve a better accordance with the chronotherapy of asthma. Each of 10 subjects was administered one tablet (equivalent to 0.1 g anhydrous theophylline) in the morning and four tablets in the evening for a consecutive 6 days and blood samples were collected at the predetermined time and analyzed by a validated HPLC method. This new regimen produced a steady and effective level of theophylline in plasma for the whole day, especially in the evening. A lower dose in the morning could reach the effective level (C(min)4.97 +/- 1.60 microg/mL and C(max)10.68 +/- 1.80 micro g/mL over the a.m. dosing interval) and a higher dose in the evening did not result in toxic levels but led to a reasonable concentration range (C(max)9.72 +/- 1.56 microg/mL over p.m. dosing interval), which could maintain a higher plasma theophylline concentration without the risk of serious adverse events and control asthmatic symptoms probably occurring during the night or early in the morning. The results suggested that the proposed asymmetric regimen was necessary, practicable and safe for twice daily sustained-release tablets of theophylline sodium glycerinate and also provides the basis for the clinical dosage regimen of other theophylline formulated products.