Pharmacokinetic study of free‐form sinomenine in rat skin by microdialysis coupled with liquid chromatography–electrospray mass spectrometry

Abstract

Sinomenine (7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one) is a pure alkaloid extracted from the Chinese medical plant. In this report a liquid chromatography-electrospray mass spectrometry (LC-ESI-MS) method with in vivo microdialysis for the pharmacokinetic study of free-form sinomenine in rat skin has been developed. A microdialysis probe was surgically implanted into the subcutaneous tissue of the rats and an isotonic phosphate buffer (PBS) was used as the perfusion medium. Samples were collected and then analyzed off-line by LC-ESI-MS. The chromatographic separation was achieved within 4.2 min by using a narrow-bore Xterra C(18) column (2.1 x 150 mm, 5 microm) with acetonitrile-(10 mmol/L ammonium acetate buffer, 0.1% acetic acid) (15:85, v/v). Ion signal m/z 330.1 for sinomenine was measured in the positive mode. Linearity was established for the range of concentrations of 2.0-10000.0 ng/mL with a coefficient of determination (r) of 0.9989. The intra- and inter-day reproducibility of the present method was better than 6%. The lower limit of quantification (LLOQ) was 1.0 ng/mL. The proposed method described provides more authentic information on pharmacokinetics and metabolism at the site of action by using the coupling of microdialysis to LC-ESI-MS technique than the traditional sampling methods.

Determination of oxymatrine and its metabolite matrine in rat blood and dermal microdialysates by high throughput liquid chromatography/tandem mass spectrometry

“…Microdialysis is a reliable and useful technique for investigation of percutaneous absorption and dermal metabolism. For instance, two unknown substances, suspected to be the metabolites of sinomenine, mostly demethyl and hydroxylated derivatives of sinomenine were found in skin microdialysates from the rats which were administered sinomenine [23,24]. Our results, although determined only in five rats, showed that the extent of metabolised OMT in the skin was rather low in relation to the amount which penetrated through the skin.…”

Determination of sinomenine sustained-release capsules in healthy Chinese volunteers by liquid chromatography–tandem mass spectrometry

“…Several liquid-liquid extractions or protein precipitation procedures [14][15][16][17][18][19][20][21][22] were exploited for plasma sample preparation. Acetonitrile, methanol and 7% perchloric acid were chosen and tested for protein precipitation because of high throughput characteristics and the suitable sensitivities obtained.…”

“…Furthermore, the lower limits of quantitation (LLOQ) of these methods in a range of 6-320 ng/mL were not suitable for sinomenine pharmacokinetic study. Some more sensitive methods using LC/MS have been reported to detect this drug in rat's brain [20] or skin [21]. Only one study using ion trap mass spectrometry has been published for the determination of sinomenine in human plasma with an LLOQ of 0.5 ng/mL [22], but the analyses were performed only with spiked plasma samples so pharmacokinetic parameters were not available.…”