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Triglyceride lowering effect of MaxEPA fish lipid concentrate: a multicentre placebo controlled double blind study.

A multicentre, double blind, randomised between-group study comparing the triglyceride lowering effect of MaxEPA, a natural marine oil, and a placebo control is described. Eighty-six patients with hypertriglyceridaemia (fasting serum triglyceride greater than or equal to 2 mmol/l) were studied for three months. There were no significant differences between the groups (48 active, 38 control) in respect of age, sex, height or weight, smoking habits or alcohol consumption. After one month triglyceride levels were reduced significantly from baseline in the treatment group and there was also a highly significant difference between the groups in favour of the marine oil. There was no significant change in serum total cholesterol in either group but there were fluctuations in high density lipoprotein (HDL) in both groups. Minor gastrointestinal side effects were reported by patients in both groups. Standard haematological and biochemical tests were done and there were no significant changes from baseline.

Adolescent↗

Lipid metabolism in Norplant-2 users--a two-year follow-up study. Total cholesterol, triglycerides, lipoproteins and apolipoproteins.

Changes in lipid metabolism in 25 healthy female volunteers during a 24-month application of Norplant-2 were evaluated in an open clinical trial. Total serum cholesterol decreased significantly (p less than 0.05/p less than 0.05) by 10%/9% after 12 months and by 3%/7% (n.s./n.s.) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). Serum triglycerides decreased by 34%/28% (n.s./p less than 0.05) after 12 months and by 29%/25% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). HDL-cholesterol decreased significantly by 18%/12% (p less than 0.01/p less than 0.05) after 12 months and by 12%/12% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). No statistically significant difference between serum levels of LDL-cholesterol prior to and after 12 and 24 months of Norplant-2 use could be found. VLDL-cholesterol levels decreased significantly by 38%/38% (p less than 0.05) after 12 and by 25%/25% after 24 months of Norplant-2 application (p less than 0.01) (all subjects/subjects completing 24 cycles). Apolipoprotein Al decreased significantly by 23%/23% (p less than 0.001/p less than 0.01) after 12 and by 21%/22% after 24 months of Norplant-2 application (p less than 0.01/p less than 0.01) (all subjects/subjects completing 24 cycles). No statistically significant difference between apolipoprotein All levels prior to and after 12 and 24 months of Norplant-2 implantation could be found. Apolipoprotein B decreased significantly by 27%/17% (p less than 0.05/p less than 0.05) after 12 months of Norplant-2 application (all subjects/subjects completing 24 cycles). The decline after 24 months of Norplant-2 use was not significant. Changes in lipid metabolism caused by oral hormonal contraceptives differ in the various clinical trials; however, most investigators found that serum levels of total cholesterol and triglycerides increase under the application of OCs. Contrary to this, a decrease of total cholesterol and triglycerides under Norplant-2 use was noted. Furthermore, we found a significant decrease of lipoproteins and apolipoproteins--with the exception of LDL-cholesterol and apolipoprotein All, which did not show any significant modifications. Thus, Norplant-2 seems to be non-contributory to cardiovascular risk and might even provide protection against such risks.

Adult↗

Effects of oral contraceptive pills on serum lipoproteins and triglycerides.

Possible effects of a combined oral contraceptive (femenal) on blood triglycerides and high-density-lipoprotein-cholesterol (HDL-Chol) were studied in 25 women who had opted for hormonal contraception. Total serum triglycerides of 64.60 +/- 12.39 mg/dl (mean +/- SD) obtained prior to the commencement of hormonal contraception, did not reveal any statistical difference from the value of 65.49 +/- 7.96 mg/dl obtained after 9 months contraception. Similarly, precontraception HDL-Chol value of 58.05 +/- 6.58 mg/dl was also not statistically different from the treatment value of 58.82 +/- 5.42 mg/dl. Regression analysis of the values between control (precontraception) and treatment (9 months contraception) showed high correlation coefficients: (1) serum triglycerides, R2 = 0.5201; P less than 0.001; (2) serum HDL-Chol, R2 = 0.6590; P less than 0.001. Both the mean body weight and blood pressure of the study subjects remained unchanged after 9 months continuous use of femenal for contraception.

Adult↗

Removal of fatty acid labelled cholesterol ester, phospholipid and triglyceride from atherosclerotic rabbit aorta in vitro.

An organ culture technique was used to investigate the removal of fatty acids incorporated into various lipid fractions in intimal segments of atherosclerotic rabbit aorta. Segments of aorta were pulse-labelled in vitro with [9,10-3H]oleic acid and [1-14C]linoleic acid for 24 h. The incubation medium was replaced with non-radioactive medium and the removal of the endogenously labelled phospholipid, triglyceride and cholesterol ester was followed for a further period of 10 days. Fatty acids incorporated into phospholipid and triglyceride were removed rapidly from the aortic intima, with fractional half-times of 4--5 days. Cholesterol ester fatty acids were removed more slowly from the aortic intima with fractional half-times of 9--12 days. When the removal rate of oleic acid incorporated into phospholipid, triglyceride and cholesterol ester was compared with that of linoleic acid incorporated into the same lipid fractions, no difference between removal of the two fatty acids could be detected with respect to any of the 3 lipid fractions.

Animals↗

The fatty acid pattern of triglycerides and FFA in serum of spontaneously hypertensive rats (SHR).

The fatty acid patterns of serum triglycerides and FFA in SHR and in normotensive controls aged 4, 8 and 26 weeks were estimated by gas-liquid chromatography. In serum triglycerides of SHR, the percentage of linoleic acid (C18:2) was lower and the content of arachidonic acid (C20:4) higher than in age-matched control animals. A continuous increase in palmitic (C16) and linoleic acids as well as a decrease in arachidonic acid has been found with advancing age, the most striking differences existing between 4- and 8-week-old animals, i.e. before onset of arterial hypertension in SHR. In the pre-hypertensive stage, the percentage of arachidonic acid was about 3 times as high as in later stages in SHR. This gradation was, however, even more pronounced in normotensive control rats. The C18:2/C20:4-ratio of triglycerides was lower in SHR but increased with age in both groups reaching a 5--8-fold level. Similar behavior of the FFA fatty acid pattern was less marked. Alterations in levels of linoleic and arachidonic acids are of interest because of their pathogenic role as precursors of prostaglandins in the development of genetically spontaneous hypertension in rats. The results are discussed in connection with the hypotensive effect of a linoleic acid-rich diet recently reported in hypertensive rats.

Age Factors↗

Plasma levels of VLDL- + LDL-cholesterol, HDL-cholesterol, triglycerides and apoproteins B and A-I in a healthy population--influence of several risk factors.

Plasma apo B and apo A-I were determined in 477 subjects (206 males and 271 females) by laser immuno-nephelometry. Measurements of VLDL- + LDL-cholesterol, HDL-cholesterol and triglycerides were done simultaneously. VLDL- + LDL-cholesterol and apo B values were similar in males and females and increased with age. HDL-cholesterol and apo A-I values were higher in females but stable with age. Different regression curves (HDL-cholesterol vs apo A-I) were obtained in males and females and a negative correlation was found between HDL-cholesterol or apo A-I and triglycerides. Increased body weight was associated with higher values of VLDL- + LDL-cholesterol, apo B and triglycerides in both sexes but lower values of HDL-cholesterol and apo A-I essentially in males. Finally, the study provides evidence of a relationship between smoking and alcohol consumption on the one hand, and HDL-cholesterol and apo A-I on the other.

Adult↗

Intra-individual variation of serum cholesterol, triglycerides and high density lipoprotein cholesterol in normal humans.

The intra-individual variation in the concentrations of serum cholesterol, triglycerides and high density lipoprotein cholesterol (HDL-chol) was determined in 53 healthy subjects, without extreme standardization of test subjects and sampling conditions. Within 1 year, the intra-individual variation of the subjects ranged from 3.9 to 10.9% for cholesterol; from 12.9 to 40.8% for triglycerides, and from 3.6 to 12.4% for HDL-chol. More than 60% of the average total intra-individual variation was caused by biological fluctuations and the remainder was the result of analytical variation. Thus, a single measurement of these serum constituents in an individual can be misleading or meaningless, unless the value is considerably outside the normal range. No significant diurnal variation was found in the concentrations of serum cholesterol and HDL-chol. The maximal post-prandial increase of the serum triglycerides was twice as great in the men than in the women. Finally, significant trends in the fluctuations of serum lipids and HDL-chol during 1 year were not found.

Adult↗

Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride.

Increased plasma insulin and triglycerides and decreased high density lipoprotein concentrations are primary risk factors in the development of coronary artery disease. The aim of the present study was to verify whether there was an independent relationship between plasma insulin levels and both HDL cholesterol and triglyceride in a worker population of 607 subjects, 389 men and 218 women, aged 23-73 years. An oral glucose tolerance test (75 g) was performed. Plasma glucose, insulin, triglyceride and HDL cholesterol were measured at fasting, plasma glucose and insulin were determined also 1 h and 2 h after glucose load. The results, examined separately in men and women documented a significant negative relationship between plasma insulin and HDL cholesterol level, as well as pointing out that both HDL cholesterol and insulin are significantly correlated to degree of hypertriglyceridemia, degree of obesity and level of glucose tolerance. The partial correlation coefficients between HDL cholesterol and plasma insulin levels at fasting in men and post-glucose load in women, demonstrated an independent relationship between increased plasma insulin and decreased plasma HDL concentration. However, the strongest relationship, revealed by partial correlation coefficient analysis, was between the degree of hyperinsulinemia and hypertriglyceridemia.

Adult↗

Serum triglycerides are a risk factor for myocardial infarction but not for angina pectoris. Results from a 10-year follow-up of Uppsala primary preventive study.

At a follow-up 7-10 years after a health survey of men born in 1920-1924 in the municipality of Uppsala, 31 of the participants (n = 2322) had died from ischaemic heart disease (IHD). In response to a letter to all men alive in 1980, 106 men declared that they had had a myocardial infarction (MI) (verified or suspected). In 58 cases MI was verified from the hospital records. 28 other men had had typical central chest pain (angina pectoris) only. In another 20 men other diagnoses explained the chest pain for which they were treated in hospital. The health screening values for S-cholesterol and S-triglycerides, blood pressure and smoking habits were analysed in relation to the occurrence of IHD. In this prospective study, smoking, hypertension, S-cholesterol and S-triglycerides were identified as risk factors for fatal and non-fatal MI. The risk factor values were similar in subjects suffering from angina pectoris only to those in subjects who also developed ECG and/or transferase changes, with the exception of S-triglyceride concentration, which was normal in the group with angina pectoris. The subjects who had a fatal MI had a significantly higher blood pressure than those with non-fatal MIs, but otherwise these two groups did not differ. The results emphasize the importance of scrutinizing questionnaire data with regard to chest pain and of selection of end-points when risk factor patterns are described for cardiovascular diseases.

Aged↗

In vitro clearance of chylomicron triglycerides containing (omega-3) eicosapentaenoate.

Rat mesenteric lymph chylomicrons, containing triglycerides enriched with either [14C]oleic acid or [14C]eicosapentaenoic acid, were prepared by ultracentrifugation of lymph samples collected for 6 h after a single duodenal infusion of an emulsion containing 0.3 mmol of either fatty acid. After determination of protein and of total fatty acid content and composition, enriched chylomicrons were suspended in Krebs-bicarbonate buffer. Non-working hearts were perfused in a recirculating system for 45 min using the enriched chylomicron preparations. At 15 min intervals during perfusion, the media were assayed for total radioactivity, 14CO2 and 14C-labeled fatty acids associated with triglycerides, unesterified fatty acids, phospholipids, mono- and diglycerides. After perfusion, the hearts were extracted and assayed for total lipid radioactivity and isotope distribution among heart lipid fractions. With this membrane-supported lipoprotein lipase system, clearances of chylomicron triglycerides containing either fatty acid were identical, as were the myocardial uptakes of the fatty acids and oxidations to 14CO2. Furthermore, except for a significantly greater incorporation of eicosapentaenoate into myocardial phospholipids, tissue isotope distributions of the two labeled fatty acids were also the same. These studies suggest that at least the initial phases of peripheral clearance of chylomicrons enriched in omega-3 fatty acids is as efficient as with those containing oleate.

Animals↗

Plasma lipoprotein lipids in relation to the MspI polymorphism of the apolipoprotein AII gene in Caucasian men. Lack of association with plasma triglyceride concentration.

Digestion of the human apolipoprotein (apo) A-II gene with the endonuclease MspI produces fragments of 3.0 or 3.7 kb, reflecting the presence or absence of a polymorphic site within an Alu sequence 3' to the gene. Patients with hypertriglyceridemia have been shown to have an increased prevalence of the 3.0 kb allele. To explore this observation further, plasma lipoprotein lipids were studied in a random sample of fasted middle-aged Caucasian men, of which 59 were 3.0 kb homozygotes, 24 were heterozygotes, and 2 were 3.7 kb homozygotes. After adjusting for the effects of age, height, weight, alcohol intake and cigarette consumption by covariance analysis, no statistically significant associations were present between genotype and the concentrations of triglyceride in whole plasma or the d less than 1.019 g/ml fraction of plasma (i.e., VLDL + IDL). Nor were the cholesterol concentrations in VLDL + IDL, low density lipoprotein (LDL, d = 1.019-1.063 g/ml), high density lipoprotein (HDL), HDL2 or HDL3 related to genotype. In an independent comparison of eight 3.0 kb homozygotes and eight 3.7 kb homozygotes (all Caucasians) drawn from a different community, genotype was unrelated to the triglyceride or cholesterol concentrations in VLDL (d less than 1.006 g/ml), IDL + LDL (d = 1.006-1.063 g/ml) or HDL, after adjustment for the effects of covariates. These results suggest that the MspI polymorphism of the apo A-II gene is not associated with genetic variation that significantly affects triglyceride transport in the majority of men.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-II↗

Interrelationship of plasma triglyceride and coagulant factor VII levels in normotriglyceridemic hypercholesterolemia.

We have evaluated the potential relationships between plasma levels of certain coagulation factors, i.e. factor VII antigen (F VIIag) and factor VII coagulant activity (F VIIc), and parameters of lipid transport in a group of 90 normotriglyceridemic patients displaying hypercholesterolemia (Fredrickson's type IIa hyperlipoproteinemia). Levels of factor VIIc were significantly elevated (P less than 0.01) in this patient group as compared to a group of healthy normolipidemic subjects. By contrast, levels of factor VIIag were also increased, but such differences were not significant in relation to those of controls. Furthermore, concentrations of F VIIc and F VIIag in hypercholesterolemic males and females resembled each other. Similar observations were made when patients were divided into those either presenting or lacking symptoms of vascular disease. However, plasma levels of both F VIIc and F VIIag were positively correlated with circulating triglyceride concentrations in the hypercholesterolemic group, but not with other parameters of lipid transport such as serum cholesterol, HDL-cholesterol, and apolipoprotein B. When patients were treated with a lipid-lowering agent (cholestyramine), lower levels of both F VIIc and F VIIag were found concomitantly with a decrease of similar order in triglyceride concentrations. We conclude that serum triglyceride levels, even within the normal range, may be associated with elevation in the activity of factor VII in hypercholesterolemic patients, thereby increasing their risk of thrombosis.

Adult↗

Effect of gemfibrozil on the concentration and composition of serum lipoproteins. A controlled study with special reference to initial triglyceride levels.

We investigated the modulating effect of serum total triglycerides on the lipid composition of various lipoproteins, and on the response to gemfibrozil treatment. This placebo controlled study was conducted blind in 60 participants of the Helsinki Heart Study. An inverse relationship was observed between cholesterol content in all lipoprotein fractions and serum total triglyceride level. Gemfibrozil, in addition to changing the absolute amounts of lipoprotein lipids, also normalized the qualitative abnormalities associated with hypertriglyceridemia. Gemfibrozil increased the level of HDL-cholesterol with the main effect on HDL3-subfraction. The observed reduction in LDL-cholesterol was dependent on the initial triglyceride level.

Cholesterol, HDL↗

Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipoprotein-lipase deficiency.

A high factor VII coagulant activity (VIIc), a marker of increased risk of coronary heart disease, is frequently found in types IIb and IV hyperlipidaemia, but its cause is not fully understood. Factor VII can be activated by factor XIIa, generated from factor XII upon activation of the contact system of coagulation. Ten patients with familial lipoprotein-lipase (LPL) deficiency and 10 healthy control subjects were therefore compared to explore the hypothesis that high concentrations of unesterified fatty acids (UFA), released from triglyceride-rich lipoproteins by LPL, are a source of factor XII activation and hence the increased VIIc that is observed post-prandially and in non-LPL-deficient hypertriglyceridaemic states. Mean plasma cholesterol and triglyceride concentrations were, respectively, 1.5- and 19-fold higher in the patients than controls, due to increases in very-low-density lipoproteins and chylomicrons. The concentration and composition of plasma UFA were similar in both groups. In conformity with the hypothesis, VIIc was not increased in the LPL-deficient group, despite their massive hypertriglyceridaemia. Furthermore, when the patients' plasma was treated with LPL, factor XII was activated promptly and substantially, whereas no similar effect was observed in the controls. These results suggest that high concentrations of circulating triglyceride-rich lipoproteins will increase VIIc in the presence of LPL.

Adult↗

Plasma triglycerides and lipoprotein(a): inverse relationship in a hyperlipidemic Italian population.

The relationship between plasma lipoprotein(a) (Lp(a)) levels and other clinical/biochemical variables was investigated in 1200 consecutive hyperlipidemic patients. Plasma Lp(a) concentrations were measured by a sandwich-ELISA method, while the patients were either on diet or diet plus lipid-lowering drugs; 38% of them had a plasma Lp(a) level > 30 mg/dl. The median plasma Lp(a) concentration and the frequency of Lp(a) > 30 mg/dl were significantly lower in individuals with severe hypertriglyceridemia vs. hypercholesterolemics (HC) or mixed hyperlipidemics (M-HLP), but similar to normolipidemic healthy controls. Patients with isolated moderate hypertriglyceridemia had Lp(a) levels intermediate between HC and M-HLP subjects. The in vitro addition of triglyceride-rich lipoproteins to normotriglyceridemic plasma did not affect the Lp(a) measurement. Plasma Lp(a) concentrations in the whole hyperlipidemic population correlated negatively with triglycerides and positively with total cholesterol, HDL-cholesterol and age, being unrelated to either body mass index or lipid-lowering treatment. In HC patients, the presence of tendon xanthomas was associated with twofold higher Lp(a) levels. These findings argue for a regulatory role of triglycerides on plasma Lp(a) levels in hyperlipidemic patients.

Adult↗

Triglyceride-rich lipoproteins of subjects heterozygous for apolipoprotein E2(Lys146-->Gln) are inefficiently converted to cholesterol-rich lipoproteins.

The APOE*2(Lys146-->Gln) allele behaves like a dominant trait in the expression of familial dysbetalipoproteinemia (FD) (Smit et al., J. Lipid Res. 1990; 31: 45-53). FD patients carrying the APOE*2(Lys146-->Gln) allele exhibit less elevated cholesterol to triglyceride ratios in the d < 1.019 g/ml lipoprotein density fraction as compared to classical FD patients displaying homozygosity for the APOE*2(Arg158-->Cys) allele (0.8 vs. 1.4). Upon treatment of complete serum with lipoprotein lipase (LPL), the mean cholesterol to triglyceride molar ratio of the d < 1.019 g/ml lipoprotein fraction in these FD patients increased only marginally (from 0.8 to 1.1), as compared with that of classical FD subjects (from 1.4 to 2.6) and non-FD control subjects (from 0.7 to 1.5). In order to obtain further evidence for an inefficient lipolysis of the d < 1.019 g/ml lipoprotein fraction in APOE*2(Lys146-->Gln) carriers, possibly in combination with a less efficient cholesteryl ester transfer protein (CETP) activity, blood samples of APOE*2(Lys146-->Gln) allele carrying FD patients were analysed and compared with classical FD patients and controls. In the APOE*2(Lys149-->Gln) allele carrying FD patients were analysed and compared with classical FD patients and controls. In the APOE*2(Lys146-->Gln) FD patients, the increase in plasma cholesterol was mainly confined to the very low density lipoprotein (VLDL) fraction, whereas in classical FD patients, the levels of cholesterol in the intermediate density lipoprotein (IDL) fraction was also dramatically increased (ratios of VLDL to IDL cholesterol are 4.7 and 2.6, respectively). Family analyses of the APOE*2(Lys146-->Gln) FD subjects showed that the apo E to apo B ratio in the d < 1.019 g/ml lipoprotein fraction of allele carriers is 3.5 times as high as that found in non-carriers (2.8 vs. 0.8, by wt.). Also, in the APOE*2(Lys146-->Gln) allele carrying family members, the ratio of cholesterol to triglyceride of the d < 1.019 g/ml lipoprotein fraction is less markedly elevated upon addition of LPL when compared to that in non-carrying controls (from 1.1 to 1.8 vs 0.7 to 1.6). The efficiency of the d < 1.019 g/ml lipoprotein fraction of APOE*2(Lys146-->Gln) FD patients to compete with low density lipoprotein (LDL) for binding to the LDL receptor is intermediate to that of controls and classical APOE*2(Arg158-->Cys) homozygous FD patients. These findings suggest that in APOE*2(Lys146-->Gln) allele carriers, the conversion of VLDL into IDL is impaired due to an inefficient lipolysis, possibly in combination with a retarded CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Triglyceride enriched lipoprotein particles correlate with the severity of coronary artery disease.

A group of 100 male normotensive, non-obese, non-diabetic subjects who had undergone coronary angiography were studied to determine relationship between the severity of coronary artery disease (CAD) and plasma lipids, apolipoproteins and lipoprotein particles defined by their apolipoprotein composition. CAD was found in 84 and no measurable lesions were found in 26 subjects. The severity of CAD was determined on the basis of size and number of lesions and expressed in terms of a global CAD score. Low density lipoprotein (LDL)-cholesterol showed a tendency to be higher in CAD patients than in CAD-free subjects (216 vs. 205 mg/dl, P = 0.07). HDL-cholesterol showed a tendency towards lower values in CAD patients compared to CAD-free subjects 35 vs. 41 mg/dl, P = 0.07). In univariate analysis the severity of CAD correlated with (i) complex, apolipoprotein (apo) B containing particles (Lp-B-complex, r = 0.31, P = 0.005), (ii) HDL-cholesterol (r = -0.30, P = 0.005), (iii) apoC-III in heparin precipitate (r = 0.30, P = 0.005) and (iv) plasma triglycerides (r = 0.25, P = 0.02), all of which are related to triglyceride-rich lipoproteins. A comparison between the two subspecies of complex lipoprotein particles revealed that those containing apolipoproteins B, C-III and E (Lp-B:C:E complex) were more closely associated with CAD score (r = 0.27, P = 0.01) than those containing apolipoproteins A-II, B, C, D and E (Lp-A-II:B-complex). LDL-cholesterol also correlated with the global CAD score (r = 0.23, P = 0.03). In multiple regression analysis only HDL-cholesterol (P = 0.003), apoC-III-ratio (P = 0.007), Lp-B-complex (P = 0.02) and Lp-B:C:E-complex (P = 0.04) showed significant correlation with CAD score. The results of this study demonstrate that some of the triglyceride rich lipoprotein particles represent a risk factor for CAD and support the clinical usefulness of specific assays capable of distinguishing lipoprotein particles on the basis of apolipoprotein composition.

Adult↗

Determination of the triglyceride composition of avocado oil by high-performance liquid chromatography using a light-scattering detector.

The triglyceride composition of avocado oil was determined by high-performance liquid chromatography using a light-scattering detector. Two avocado varieties, Fuerte and Hass, were analysed, and the qualitative composition of each was found to be similar, though quantitative differences were detected. The triglyceride composition was predicted using a system of equations based on the relationship between log k' and the molecular variables equivalent carbon number, chain length and number of double bonds for each of the fatty acids in the glycerides. A total of 24 molecular species of triglycerides were identified. The chromatographic system used successfully separated the critical pairs OOO-LOS, PaPaO-LnPP and PaOO-LOP (O = olein; L = linolein; S = stearin; Pa = palmitolein; Ln = linolenin; P = palmitin). Detector response was found to have a linear relationship with the amount of sample injected over the injection range 10-70 micrograms.

Chromatography, High Pressure Liquid↗