Ethnopharmacological　relevance　Isoboldine　is　one　of　the　major　bioactive　constituents　in　the　total　alkaloids　from　Radix　Linderae　(TARL)　which　could　effectively　alleviate　inflammation　and　joints　destruction　in　mouse　collagen-induced　arthritis.　To　better　understand　its　pharmacological　activities,　we　need　to　determine　its　pharmacokinetic　and　metabolic　profiles.　Materials　and　methods　In　this　study,　a　sensitive　and　simple　UPLC-MS/MS　method　was　developed　and　validated　for　determination　of　isoboldine　in　rat　plasma.　Isoboldine　in　plasma　was　recovered　by　liquid-liquid　extraction　using　1　mL　of　methyl　tert-butyl　ether.　Chromatographic　separation　was　performed　on　a　C18　column　at　45°C,　with　a　gradient　elution　consisting　of　acetonitrile　and　water　containing　0.1%　(v/v)　formic　acid　at　a　flow　rate　of　0.3　mL/min.　The　detection　was　performed　on　an　electrospray　triple-quadrupole　MS/MS　by　positive　ion　multiple-reaction　monitoring　mode.　This　newly　developed　method　was　successfully　applied　to　a　pharmacokinetic　study　after　oral　and　intravenous　dosing　in　rats.　For　metabolites　identification,　isoboldine　was　orally　administered　to　rats　and　the　metabolite　in　plasma,　bile,　urine　and　feces　were　characterized　by　the　established　UPLC-MS/MS　method.　Results　Good　linearity　(r2＞0.9956)　was　achieved　in　a　concentration　range　of　4.8-2400　ng/mL　with　a　lower　limit　of　quantification　of　4.8　ng/mL　for　isoboldine.　The　intra-　and　inter-day　precisions　of　the　assay　were　1.7-5.1%　and　2.2-4.4%　relative　standard　deviation　with　an　accuracy　of　91.3-102.3%.　A　total　of　five　phase　II　metabolites　in　rat　plasma,　bile,　urine　and　feces　were　characterized　by　comparing　retention　time　in　UPLC,　and　by　molecular　mass　and　fragmentation　pattern　of　the　metabolites　by　mass　spectrometry　with　those　of　isoboldine.　Conclusion　isoboldine　has　extremely　low　oral　bioavailability　due　to　the　strong　first-pass　effect　by　the　rats,　and　glucuronidation　and　sulfonation　were　involved　in　metabolic　pathways　of　isoboldine　in　rats.　These　results　have　paved　the　way　for　further　clarifying　therapeutic　ingredients　and　provided　new　knowledge　regarding　pharmacokinetic　features　of　this　category　of　isoquinoline　alkaloids.　©　2015　Elsevier　Ireland　Ltd.　All　rights　reserved.