Quantification of the 15 major human bile acids and their precursor 7α-hydroxy-4-cholesten-3-one in serum by liquid chromatography–tandem mass spectrometry

Steiner, Carine; Eckardstein, Arnold von; Rentsch, Katharina

doi:10.1016/j.jchromb.2010.08.045

Cited by 76 publications

(66 citation statements)

References 26 publications

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“…The use of MS operating in the MRM mode enabled the accomplishment of high sensitivity, reliable quantifi cation, and a wide dynamic range. The proposed instrumental confi guration offers a key advantage over other MS methods ( 13,21,35 ), allowing the profi ling of a larger number of BAs. Moreover, the high sensitivity attained, if compared with other previously reported methods ( 20-24, 28, 30, 36 ), considerably reduces sample requirements because now 25 l of serum and 5 mg of liver tissue suffi ce to perform proper BA profi ling.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in BA profi les can be used as biomarkers of disease ( 10,17,18 ), and, therefore, accurate and sensitive techniques are required for the comprehensive profi ling BAs, including those found at relatively low concentrations in physiological conditions. A number of LC/MS methods have been developed for this purpose, but their extensive sample processing and their limited capacity to detect minor BAs ( 11,(19)(20)(21)(22)(23)(24)(25) have restrained their use. In fact, detection of low-concentrated or unusual BAs in human samples, is an important target of BA profi ling given their important role in some pathological situations ( 10,13,26 ).…”

Section: Uplc-ms Analysismentioning

confidence: 99%

“…Then endogenous BAs were stripped off by activated charchoal incubation, as previously described ( 21 ). Next, known amounts of individual BAs were added to the prepared BA free matrices and to a blank matrix consisting in methanol:water (50:50, v/v).…”

Section: Sample Collectionmentioning

confidence: 99%

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Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method

García-Cañaveras

Donato

Castell

et al. 2012

Journal of Lipid Research

236

190

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Section: Discussionmentioning

confidence: 99%

Section: Uplc-ms Analysismentioning

confidence: 99%

See 1 more Smart Citation

Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method

García-Cañaveras

Donato

Castell

et al. 2012

Journal of Lipid Research

236

190

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“…Individual bile acid concentrations in plasma (day 14), bile, and frozen liver samples (day 14) were quantifi ed by capillary gas chromatography and further characterized by LC-MS/MS as described previously (16)(17)(18). Plasma 7 ␣ -hydroxy-4-cholesten-3-one (C4) concentrations were determined as described previously ( 19 ). Plasma bile acid pool was calculated as the product of plasma total bile acid concentration ( M) and blood volume assuming 80 ml/kg body weight.…”

Section: Immunoblot Analysismentioning

confidence: 99%

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

Vlaardingerbroek

Stoll

et al. 2014

Journal of Lipid Research

116

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Cholestatic liver disease is one of the most common metabolic problems associated with total parenteral nutrition (TPN) in preterm infants, and it is strongly related to the duration of TPN ( 1 ). The incidence of parenteral nutrition-associated liver disease (PNALD) in infants who Abstract Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fi sh oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fi sh oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14 day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7 ␣ -hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OST ␣ ) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both This work was supported in part by federal funds from the USDA,, the American Society for Parenteral and Enteral Nutrition, Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSEP, bile salt export pump; CA, cholic acid; CDCA, chenodeoxycholic acid; C4, 7 ␣ -hydroxy-4-cholesten-3-one; CYP8B1, sterol 12-alpha-hydroxylase; CYP7A1, cholesterol 7-hydroxylase; CYP3A29, cytochrome P450 3A29; CYP27A1, sterol 27-hydroxylase; FGF, fi broblast growth factor; FXR, farnesoid X receptor; GGT, gamma glutamyl transferase; MCT, medium chain triglyceride; MRP3, multidrug resistant protein 3; NTCP, Na + / taurocholate cotransporter; OBCA, obeticholic acid; OST ␣ / ␤ , organic solute transporters alpha and beta; PNALD, parenteral nutrition-associated liver disease; TPN, total parenteral nutrition; UDCA, ursodeoxycholic acid . and immediately placed in cages housed at 31°C to 32°C, as described previously ( 12 ). Based on body weight, pigs delivered from each sow were randomly assigned to one of the three TPN treatment groups or to enteral nutrition (ENT). After delivery, pigs were surgically implanted with catheters into the jugular vein and umbilical artery. Pigs in the enteral group also were implanted with an orogastric feeding tube, whereas TPN groups received a sham puncture. Maternal plasma (16 ml/kg intravenously during the fi rst 24 h) was administered for passive immunological protection. During the 14 day study, pigs received antibiotics (enrofl oxacin 5 mg/kg) intrave...

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“…Surprisingly, T-CDCA, T-DCA, T-LCA, T-b-MCA and T-UDCA reached LLOQs at the pM range and are remarkably lower than those of previous studies (Table 3). 18,23 This can be explained by employing MRM and using specic fragments for quantication of BAs, thereby reducing the SNR in the second mass lter and improving sensitivity. Recently, García-Cañaveras et al reported comparable LLOQs for a number of unconjugated BAs in 25 mL of sample volume using SIM operated in negative ion mode, differences that are likely to be caused by different sensitivities of the instruments used.…”

Section: -23mentioning

confidence: 99%

Quantification of multiple bile acids in uninephrectomized rats using ultra-performance liquid chromatography-tandem mass spectrometry

et al. 2013

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In order to study the roles of individual BAs and due to limited blood sample volumes available from experimental animals, improved methods for the simultaneous quantification of multiple BAs are needed. We developed and validated an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantification of 24 BAs, including 11 unconjugated, 6 glycine-conjugated and 7 taurine-conjugated BAs, in 50 mL of rat serum or plasma. The UPLC-MS/MS method, operated in negative and positive ion mode, allows quantification of BAs using multiplereaction monitoring (MRM), with specific fragmentation of BAs. The method showed acceptable intraand inter-day accuracy, precision, extraction recovery and high sensitivity, with a lower limit of quantification (LLOQ) in the pM range for several taurine-conjugated BAs. We applied the established method to investigate potential time-dependent changes of BAs in plasma from sham-operated and uninephrectomized male Sprague-Dawley rats. The levels of several primary and secondary BAs were transiently elevated one week after uninephrectomy, followed by normalization thereafter. In contrast, several conjugated BAs were slightly increased after the second week post-surgery. The established UPLC-MS/MS method, employing specific fragmentation of free and conjugated BAs by MRM, allows the simultaneous quantification of multiple BAs in 50 mL serum or plasma samples, and can be used to assess BA profiles in patho-physiological situations.

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Quantification of the 15 major human bile acids and their precursor 7α-hydroxy-4-cholesten-3-one in serum by liquid chromatography–tandem mass spectrometry

Cited by 76 publications

References 26 publications

Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method

Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

Quantification of multiple bile acids in uninephrectomized rats using ultra-performance liquid chromatography-tandem mass spectrometry

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